5,787 results match your criteria American journal of physiology. Cell physiology[Journal]


Electrical stimulation facilitates the angiogenesis of human umbilical vein endothelial cells through MAPK/ERK signaling pathway by stimulating FGF2 secretion.

Am J Physiol Cell Physiol 2019 Apr 17. Epub 2019 Apr 17.

Department of Burns and Plastic Surgery, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.

Electrical stimulation (ES) is able to enhance angiogenesis by stimulating fibroblasts. Fibroblast growth factor 2 (FGF2) is an independent angiogenesis inducer. The current study aimed to evaluate the role of ES-induced FGF2 secretion in affecting angiogenesis during wound healing the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway. Read More

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http://dx.doi.org/10.1152/ajpcell.00474.2018DOI Listing

Differential YAP nuclear signaling in healthy and dystrophic skeletal muscle.

Am J Physiol Cell Physiol 2019 Apr 17. Epub 2019 Apr 17.

Departments of Orthopaedics and Physiology, University of Maryland School of Medicine, United States.

Mechanical forces regulate muscle development, hypertrophy, and homeostasis. Force-transmitting structures allow mechanotransduction at the sarcolemma, cytoskeleton, and nuclear envelope. There is growing evidence that YAP (Yes-associated protein) serves as a nuclear relay of mechanical signals and can induce a range of downstream signaling cascades. Read More

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http://dx.doi.org/10.1152/ajpcell.00432.2018DOI Listing

No Postage Required: Extracellular Vesicles Deliver the Message.

Am J Physiol Cell Physiol 2019 Apr 17. Epub 2019 Apr 17.

Department of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom.

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http://dx.doi.org/10.1152/ajpcell.00108.2019DOI Listing

Methylglyoxal Triggers Human Aortic Endothelial Cell Dysfunction via Modulating K/MAPK pathway.

Am J Physiol Cell Physiol 2019 Apr 17. Epub 2019 Apr 17.

Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Centers for Molecular Medicine and Genetics,Cardivascular Research Institute; Wayne State University, Detroit, MI, United States.

Endothelial dysfunction is one of the key risk factors in diabetes-related multi-organ damage. Methylglyoxal (MGO), a highly reactive dicarbonyl mainly generated as a by-product of glycolysis, is increased in both type 1 and type 2 diabetic patients. MGO can rapidly bind with proteins, nucleic acids and lipids, resulting in structural and functional changes of these targets and can form advanced glycation end products (AGEs). Read More

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http://dx.doi.org/10.1152/ajpcell.00117.2018DOI Listing

mTORC1 is required for expression of LRPPRC and cytochrome c oxidase but not HIF-1α in Leigh Syndrome French Canadian Type Patient Fibroblasts.

Am J Physiol Cell Physiol 2019 Apr 17. Epub 2019 Apr 17.

Department of Nutrition, Université de Montréal, Montréal, QC H3C 3J7, Canada. Department of Medicine, Université de Montréal, Montréal, QC H3C 3J7, Canada.

Leigh syndrome French Canadian type (LSFC) is a mitochondrial disease caused by mutations in the LRPRRC gene leading to a reduction of cytochrome c oxidase (COX) expression reaching 50% in skin fibroblasts. We have shown that, under basal conditions, LSFC and control cells display similar ATP levels. We hypothesized that this occurs through upregulation of mechanistic target of rapamycin (mTOR)-mediated metabolic reprogramming. Read More

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http://dx.doi.org/10.1152/ajpcell.00160.2017DOI Listing

Non-coding RNAs in kidney injury and repair.

Am J Physiol Cell Physiol 2019 Apr 10. Epub 2019 Apr 10.

Department of Nephrology, The Key Laboratory of Kidney Disease and Blood Purification of Hunan Province, Second Xiangya Hospital at Central South University, Changsha, Hunan, China; Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood VA Medical Center, Augusta, GA, USA.

Acute kidney injury (AKI) is major kidney disease featured by a rapid decline of renal function. Pathologically, AKI is characterized by tubular epithelial cell injury and death. Besides its acute consequence, AKI contributes critically to the development and progress of chronic kidney disease (CKD). Read More

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http://dx.doi.org/10.1152/ajpcell.00048.2019DOI Listing
April 2019
1 Read

Contractile benefits of doublet-initiated low-frequency stimulation in rat EDL muscle exposed to high extracellular [K] or fatiguing contractions.

Am J Physiol Cell Physiol 2019 Apr 10. Epub 2019 Apr 10.

Department of Public Health, Aarhus University, Aarhus, Denmark.

During dynamic contractions, high frequency muscle activation is needed to achieve optimal power. This must be balanced against an increased excitation-induced accumulation of extracellular K, which can reduce excitability and ultimately may prevent adequate responses to high frequency activation. Mean activation frequencies in vivo are often low ( sub-tetanic), but activation patterns contain bursts of high ( supra-tetanic) frequencies known as doublets, which enhance dynamic contraction in rested muscles at normal [K]. Read More

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http://dx.doi.org/10.1152/ajpcell.00519.2018DOI Listing

CORRIGENDUM.

Authors:

Am J Physiol Cell Physiol 2019 Apr;316(4):C582

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http://dx.doi.org/10.1152/ajpcell.zh0-8419-corr.2019DOI Listing

Elevated glucose concentration in culture media decreases membrane trafficking of SGLT2 in LLC-PK cells via a cAMP/PKA dependent pathway.

Am J Physiol Cell Physiol 2019 Apr 3. Epub 2019 Apr 3.

Department of Pharmaceutical Sciences St. John's University, Queens, NY 11439, United States.

Sodium-dependent glucose reabsorption in the renal proximal tubule is dynamically regulated by changes in blood glucose levels. There is however a disparity in reports studying the relationship between hyperglycemia and SGLT function and expression. Similarly, manipulation of the glucose content in growth media if cultured renal cells has been shown to influence SGLT activity. Read More

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http://dx.doi.org/10.1152/ajpcell.00433.2018DOI Listing

Age and prior exercise in vivo determine the subsequent in vitro molecular profile of myoblasts and non-myogenic cells derived from human skeletal muscle.

Am J Physiol Cell Physiol 2019 Mar 27. Epub 2019 Mar 27.

Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2400, Denmark. Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2200, Denmark.

The decline in skeletal muscle regenerative capacity with age is partly attributed to muscle stem cell (satellite cell) dysfunction. Recent evidence has pointed to a strong interaction between myoblasts and fibroblasts, but the influence of age on this interaction is unknown. Additionally, while the native tissue environment is known to determine the properties of myogenic cells in vitro, how the ageing process alters this cell memory has not been established at the molecular level. Read More

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http://dx.doi.org/10.1152/ajpcell.00049.2019DOI Listing
March 2019
1 Read

Mild hypothermia affects the morphology and impairs glutamine-induced anabolic response in human primary myotubes.

Am J Physiol Cell Physiol 2019 Mar 27. Epub 2019 Mar 27.

Department of Health Sciences, Örebro University, Örebro, Sweden.

The specific impact of reduced temperature on skeletal muscle adaptation has been poorly investigated. Cold water immersion, one situation leading to decreased skeletal muscle temperature, is commonly proposed to reduce the perception of fatigue and muscle soreness after strenuous exercise. In contrast, it may impair long-term benefits of resistance exercise training on muscle strength and hypertrophy. Read More

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http://dx.doi.org/10.1152/ajpcell.00008.2019DOI Listing
March 2019
3 Reads

Regulation of Na-K-Cl cotransporter type 2 by the with no lysine kinase-dependent signaling pathway.

Am J Physiol Cell Physiol 2019 Mar 27. Epub 2019 Mar 27.

Nephrology Research Group, L'Hôtel-Dieu de Québec Research Center, Department of Medicine, Faculty of Medicine, Laval University, Québec (QC), Canada G1R2J6.

The Na-K-Cl cotransporter type 2 (NKCC2) is confined to the apical membrane of the thick ascending limb of Henle where it reabsorbs a substantial fraction of the ultrafiltered NaCl load. It is expressed along this nephron segment as three main splice variants (called NKCC2A, NKCC2B and NKCC2F) that differ in residue composition along their second transmembrane domain and first intracellular cytosolic connecting segment (CS2). NKCC2 is known to be activated by cell shrinkage and intracellular [Cl] reduction. Read More

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http://dx.doi.org/10.1152/ajpcell.00041.2019DOI Listing

Stem Cells & Extracellular Vesicles in Physiology & Disease.

Am J Physiol Cell Physiol 2019 Mar 27. Epub 2019 Mar 27.

Division of Hematology and Oncology, Rhode Island Hospital, The Warren Alpert Medi- cal School of Brown University, Providence, RI, United States.

Many different subpopulations of subcellular extracellular vesicles (EVs) have been described. EVs are released from all cell types and have been shown to regulate normal physiological homeostasis, as well as pathological states by influencing cell proliferation, differentiation, organ homing, injury and recovery, as well as disease progression. In this review, we focus on the bi-directional actions of vesicles from normal and diseased cells on normal or leukemic target cells; and on the leukemic microenvironment as a whole. Read More

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http://dx.doi.org/10.1152/ajpcell.00017.2019DOI Listing
March 2019
1 Read

Excessive activation of NMDA receptor inhibits the protective effect of endogenous bone marrow MSCs on promoting alveolarization in bronchopulmonary dysplasia.

Am J Physiol Cell Physiol 2019 Mar 27. Epub 2019 Mar 27.

Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

We studied the role of bone marrow mesenchymal stem cells (MSCs) in our established model of bronchopulmonary dysplasia (BPD) induced by intrauterine hypoxia in rat. First, we found that intrauterine hypoxia can reduce the number of MSCs in lungs and bone marrow of rat neonates, whereas the administration of granulocyte colony-stimulating factor or busulfan to either motivate or inhibit bone marrow MSCs to lungs altered lung development. Next, in vivo experiments we confirmed that intrauterine hypoxia also impaired bone marrow MSCs proliferation and decreased cell cycling activity. Read More

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http://dx.doi.org/10.1152/ajpcell.00392.2018DOI Listing

Integrin α7 Signaling Regulates Connexin 43, M-Cadherin and Myoblast Fusion.

Am J Physiol Cell Physiol 2019 Mar 20. Epub 2019 Mar 20.

Department of Biomedical Engineering, College of Engineering, Virginia Commonwealth University, Richmond, VA. Department of Periodontics, University of Texas Health Sciences Center at San Antonio, San Antonio, TX, United States.

Regenerative medicine treatments for severe skeletal muscle injuries are limited, resulting in persistent functional deficits. Clinical options include neglecting the wound with the expectation that fibrosis will develop, or using an autologous muscle graft with minimal functional improvement. A regenerative matrix can be used, but muscle fiber development on these matrices remains a challenge in vivo. Read More

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http://dx.doi.org/10.1152/ajpcell.00282.2018DOI Listing

Identification of transmembrane protein 237 as a novel interactor with the intestinal riboflavin transporter-3 (RFVT-3): role in functionality and cell biology.

Am J Physiol Cell Physiol 2019 Mar 20. Epub 2019 Mar 20.

Departments of Physiology/Biophysics and Medicine, School of Medicine, University of California, Irvine, CA, 92697; Veterans Affairs Medical Center, Long Beach, CA, 90822, United States.

The apically localized riboflavin (RF) transporter-3 (RFVT-3) is involved in intestinal absorption of vitamin B2. Previous studies have characterized different physiological/biological aspects of the RFVT-3, but there is a lack of knowledge regarding possible existence of interacting partner(s) and consequence of interaction (s) on its function/cell biology. To address the latter, we performed yeast two-hybrid (Y2H) screening of a human colonic cDNA library and have identified transmembrane protein 237 (TMEM237) as a putative interactor with the human (h)RFVT-3; the interaction was further confirmed via "1-by-1" Y2H assay that involved appropriate positive and negative controls. Read More

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http://dx.doi.org/10.1152/ajpcell.00029.2019DOI Listing

Intestinal Epithelial Tight Junction Barrier regulation by Autophagy related protein ATG6/beclin 1.

Am J Physiol Cell Physiol 2019 Mar 20. Epub 2019 Mar 20.

Department of Medicine, College of Medicine, Penn State University, Hershey, PA 17111, United States.

Defective tight junction (TJ) barrier is a key pathogenic factor for Inflammatory Bowel Disease. Previously, we have shown that autophagy, a cell survival mechanism, enhances intestinal epithelial TJ barrier function. Autophagy related protein ATG6/beclin 1, a key protein in the autophagy pathway, also plays a role in the endocytic pathway. Read More

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http://dx.doi.org/10.1152/ajpcell.00246.2018DOI Listing
March 2019
3.780 Impact Factor

Cyp1b1-deficient retinal astrocytes are more proliferative and migratory, and are protected from oxidative stress and inflammation.

Am J Physiol Cell Physiol 2019 Mar 20. Epub 2019 Mar 20.

Departments of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI. Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI USA. Department of Biomedical Engineering, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States.

Astrocytes (AC) are the most abundant cells in the central nervous system. Retinal AC play an important role in maintaining the integrity of retinal neurovascular function, and their dysfunction contributes to the pathogenesis of various eye diseases including diabetic retinopathy. Cytochrome p450 1B1 (CYP1B1) expression in the neurovascular structures of the central nervous system including AC has been reported. Read More

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http://dx.doi.org/10.1152/ajpcell.00021.2019DOI Listing
March 2019
1 Read

Electrophysiological Impact of Thiocyanate on Isolated Mouse Retinal Pigment Epithelial Cells.

Am J Physiol Cell Physiol 2019 Mar 20. Epub 2019 Mar 20.

Department of Molecular and Integrative Physiology University of Michigan, Ann Arbor, MI, United States.

Our recent electrophysiological analysis of mouse retinal pigment epithelial (RPE) cells revealed that in the presence of 10 mM external thiocyanate (SCN), voltage steps generated large transient currents whose time-dependent decay most likely results from the accumulation or depletion of SCN intracellularly. In the present study, we investigated the effects of more physiologically relevant concentrations of this biologically-active anion. In whole-cell recordings of C57B/6 mouse RPE cells, we found that over the range of 50 to 500 µM SCN, the amplitude of transient currents evoked by voltage steps was proportional to the extracellular SCN concentration. Read More

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http://dx.doi.org/10.1152/ajpcell.00010.2019DOI Listing

The load-dependence of muscle's force-velocity curve is modulated by alternative myosin converter domains.

Am J Physiol Cell Physiol 2019 Mar 13. Epub 2019 Mar 13.

Department of Biological Sciences, Department of Biomedical Engineering & Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute 110 8th Street, Troy, NY 12180, United States.

The hyperbolic shape of the muscle force-velocity relationship (FVR) is characteristic of all muscle fiber types. The degree of curvature of the hyperbola varies between muscle fiber types and is thought to be set by force-dependent properties of different myosin isoforms. However, the structural elements in myosin and the mechanism that determines force-dependence are unresolved. Read More

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http://dx.doi.org/10.1152/ajpcell.00494.2018DOI Listing
March 2019
3 Reads

Acute increases in O-GlcNAc indirectly impairs mitochondrial bioenergetics through dysregulation of LonP1-mediated mitochondrial protein complex turnover.

Am J Physiol Cell Physiol 2019 Mar 13. Epub 2019 Mar 13.

Division of Molecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, United States.

The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function. Importantly, the O-GlcNAc modification of mitochondrial proteins has been identified as a potential mechanism to modulate metabolism under stress with both potentially beneficial and detrimental effects. This suggests that temporal and dose-dependent changes in O-GlcNAcylation may have different effects on mitochondrial function. Read More

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https://www.physiology.org/doi/10.1152/ajpcell.00491.2018
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http://dx.doi.org/10.1152/ajpcell.00491.2018DOI Listing
March 2019
8 Reads

A dileucine motif in the COOH-terminal domain of NKCC1 targets the cotransporter to the plasma membrane.

Am J Physiol Cell Physiol 2019 Apr 13;316(4):C545-C558. Epub 2019 Mar 13.

Department of Anesthesiology, Vanderbilt University School of Medicine , Nashville, Tennessee.

Na-K-2Cl cotransporter-1 (NKCC1) mediates the electroneutral transport of Na, K, and Cl and is normally localized to the basolateral membrane of polarized epithelial cells. We recently reported the first known solute carrier family 12 member 2 ( SLC12A2) mutation (we call NKCC1-DFX) that causes epithelial dysfunction in an undiagnosed disease program case. The heterozygous mutation leads to truncation of the COOH-terminal tail of the cotransporter, resulting in both mutant and wild-type cotransporters being mistrafficked to the apical membrane of polarized epithelial cells. Read More

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http://dx.doi.org/10.1152/ajpcell.00023.2019DOI Listing

Changes in the fraction of strongly attached cross bridges in mouse atrophic and hypertrophic muscles as revealed by Continuous Wave EPR.

Am J Physiol Cell Physiol 2019 Mar 13. Epub 2019 Mar 13.

Department of Chemical Sciences, University of Padova, Via F. Marzolo 1, 35131 Padua, Italy.

Electron Paramagnetic Resonance (EPR), coupled with Site-Directed Spin Labelling (SDSL), has been proven to be a particularly suitable technique to extract information on the fraction of myosin heads strongly bound to actin upon muscle contraction. The approach can be used to investigate possible structural changes occurring in myosin of fibers altered by diseases and aging. In this work, we labelled myosin at position Cys707, located in the SH1-SH2 helix in the myosin head cleft, with Iodo Acetamide Spin Label (IASL), a spin label, which is sensitive to the reorientational motion of this protein during the ATPase cycle, and characterized the biochemical states of the labelled myosin head by means of Continuous Wave EPR. Read More

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http://dx.doi.org/10.1152/ajpcell.00438.2018DOI Listing

Palmitate decreases migration and proliferation and increases oxidative stress and inflammation in smooth muscle cells. Role of the Nrf2 signaling pathway.

Am J Physiol Cell Physiol 2019 Mar 13. Epub 2019 Mar 13.

Research Unit on Lipid and Atherosclerosis, "Sant Joan" University Hospital, Universitat Rovira i Virgili, IISPV, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Reus, Spain.

Fatty acids are essential to cell functionality, and may exert diverging vascular effects including migration, proliferation, oxidative stress and inflammation. This study examined the effect of palmitate on human coronary artery smooth muscle cell (HCASMC) function. An in vitro wound-healing assay indicated that palmitate decreased HCASMC migration in dose- and time-dependent manners. Read More

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https://www.physiology.org/doi/10.1152/ajpcell.00293.2018
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http://dx.doi.org/10.1152/ajpcell.00293.2018DOI Listing
March 2019
5 Reads

MicroRNAs in Brain Development and Cerebrovascular Pathophysiology.

Am J Physiol Cell Physiol 2019 Mar 6. Epub 2019 Mar 6.

Lawrence D. Longo, MD Center for Perinatal Biology, Department of Basic Sciences Loma Linda University School of Medicine Loma Linda, California 92350, United States.

MicroRNAs (miRNAs) are a class of highly conserved non-coding RNAs with 21-25 nucleotides in length, and play an important role in regulating gene expression at the post-transcriptional level via base-paring with complementary sequences of the 3' untranslated region of the target gene mRNA, leading to either transcript degradation or translation inhibition. Brain-enriched miRNAs act as versatile regulators of brain development and function, including neural lineage and subtype determination, neurogenesis, synapse formation and plasticity, neural stem cell proliferation and differentiation, and responses to insults. Herein, we summarize the current knowledge regarding the role of miRNAs in the brain development and cerebrovascular pathophysiology. Read More

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http://dx.doi.org/10.1152/ajpcell.00022.2019DOI Listing
March 2019
3 Reads

Elevated myonuclear density during skeletal muscle hypertrophy in response to training is reversed during detraining.

Am J Physiol Cell Physiol 2019 May 6;316(5):C649-C654. Epub 2019 Mar 6.

Department of Rehabilitation Sciences, University of Kentucky , Lexington, Kentucky.

Myonuclei gained during exercise-induced skeletal muscle hypertrophy may be long-lasting and could facilitate future muscle adaptability after deconditioning, a concept colloquially termed "muscle memory." The evidence for this is limited, mostly due to the lack of a murine exercise-training paradigm that is nonsurgical and reversible. To address this limitation, we developed a novel progressive weighted-wheel-running (PoWeR) model of murine exercise training to test whether myonuclei gained during exercise persist after detraining. Read More

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http://dx.doi.org/10.1152/ajpcell.00050.2019DOI Listing

Physiological cAMP-raising secretagogues differentially regulate fluid and protein secretions in mouse submandibular and sublingual glands.

Am J Physiol Cell Physiol 2019 Mar 6. Epub 2019 Mar 6.

the Secretory Mechanisms and Dysfunction Section, Division of Intramural Research, National Institute of Dental and Craniofacial Research, National Institute of Health, Bethesda, MD 20892, USA. Facultad de Ciencias de la Salud, Universidad Arturo Prat, Iquique 1110939, Chile.

The mechanisms underlying the functional differences in sympathetic and parasympathetic regulation of the major salivary glands have received little attention. The acute effects of parasympathetic muscarinic (carbachol)-dependent and combined parasympathetic-dependent + cAMP-dependent pathways on fluid secretion rates, ion composition and protein content were assessed using a newly developed ex vivo preparation that allows the simultaneous perfusion of the mouse submandibular (SMG) and sublingual (SLG) glands. Our results confirm that the muscarinic dependent pathway accounts for the bulk of salivation in SMG and SLG while co-stimulation with a cAMP-increasing agent (forskolin, isoproterenol, or vasoactive intestinal peptide) did not increase the flow rate. Read More

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http://dx.doi.org/10.1152/ajpcell.00421.2018DOI Listing

From matrices to mitochondria: Emerging roles and regulation of the striated muscle cytoskeleton.

Am J Physiol Cell Physiol 2019 Mar 6. Epub 2019 Mar 6.

Dept of Pathology and Molecular Medicine, McMaster University. Hamilton ON, Canada. Muscle Health Research Center, York University. Toronto ON, Canada.

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http://dx.doi.org/10.1152/ajpcell.00071.2019DOI Listing

OSCC-derived exosomes promote M2-type macrophage polarization mediated by exosome-enclosed miR-29a-3p.

Am J Physiol Cell Physiol 2019 Feb 27. Epub 2019 Feb 27.

Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.

Objective This study aims to explore the mechanism of the signal transmission between oral squamous cell carcinoma (OSCC) and unpolarized macrophages by means of OSCCs-derived exosomes (OSCC-Exo). Methods Polarization of macrophage was determined by the detection of marker proteins or specific factors for M1- or M2-type macrophage. Exosomes extracted from two OSCC cell lines, which might have been transfected with miR-29a-3p inhibitor or mimic, were co-cultured with macrophage so as to ensure the effect of exosome-enclosed miR-29a-3p on macrophages polarization. Read More

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https://www.physiology.org/doi/10.1152/ajpcell.00366.2018
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http://dx.doi.org/10.1152/ajpcell.00366.2018DOI Listing
February 2019
1 Read

Rapid flow-induced activation of Gα is independent of Piezo1 activation.

Am J Physiol Cell Physiol 2019 Feb 27. Epub 2019 Feb 27.

La Jolla Bioengineering Institute, La Jolla, California, United States.

Endothelial cell (EC) mechanochemical transduction is the process by which mechanical stimuli are sensed by ECs and transduced into biochemical signals and ultimately into physiological responses. Identifying the mechanosensor/mechanochemical transducer(s) and describing the mechanism(s) by which they receive and transmit the signals has remained a central focus within the field. The heterotrimeric G protein, Gα, is proposed to be part of a macromolecular complex together with PECAM-1 at EC junctions and may constitute the mechanochemical transducer as it is rapidly activated within seconds of flow onset. Read More

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http://dx.doi.org/10.1152/ajpcell.00215.2018DOI Listing
February 2019

On the role of tubulin, plectin, desmin and vimentin in the regulation of mitochondrial energy fluxes in muscle cells.

Am J Physiol Cell Physiol 2019 Feb 27. Epub 2019 Feb 27.

Laboratory of Chemical Biology, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, 12618 Tallinn, Estonia, Estonia.

Mitochondria perform a central role in life and death of the eukaryotic cell. They are major players in the generation of macroergic compounds and function as integrated signaling pathways, including the regulation of Ca signals and apoptosis. A growing amount of evidence is demonstrating that mitochondria of muscle cells use cytoskeletal proteins (both microtubules and intermediate filaments) not only for their movement and proper cellular positioning, but also to maintain their biogenesis, morphology, function, and regulation of energy fluxes through the outer mitochondrial membrane (MOM). Read More

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http://dx.doi.org/10.1152/ajpcell.00303.2018DOI Listing
February 2019

Protein arginylation of cytoskeletal proteins in the muscle -- modifications modifying function.

Am J Physiol Cell Physiol 2019 Feb 21. Epub 2019 Feb 21.

Department of Biomedical Sciences, University of Pennsylvania, United States.

The cytoskeleton drives many essential processes in normal physiology, and its impairments underlie many diseases, including skeletal myopathies, cancer and heart failure that broadly affect the developed countries worldwide. Cytoskeleton regulation is a field of investigation of rapidly emerging global importance, and a new venue for the development of potential therapies. This review overviews our current understanding of the posttranslational regulation of the muscle cytoskeleton through arginylation, a tRNA-dependent addition of arginine to proteins mediated by the arginyltransferase Ate1. Read More

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http://dx.doi.org/10.1152/ajpcell.00500.2018DOI Listing
February 2019
1 Read

Mechanisms of Niemann-Pick type C1 Like 1 protein degradation in intestinal epithelial cells.

Am J Physiol Cell Physiol 2019 Apr 21;316(4):C559-C566. Epub 2019 Feb 21.

Jesse Brown Veterans Affairs Medical Center , Chicago, Illinois.

Intestinal Niemann-Pick C1 Like 1 (NPC1L1) protein plays a key role in cholesterol absorption. A decrease in NPC1L1 expression has been implicated in lowering plasma cholesterol and mitigating the risk for coronary heart disease. Little is known about the mechanisms responsible for NPC1L1 protein degradation that upon activation may lead to a reduction in NPC1L1 protein levels in intestinal epithelial cells (IECs). Read More

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http://dx.doi.org/10.1152/ajpcell.00465.2018DOI Listing
April 2019
8 Reads

Possible involvement of 4-hydroxy-2-nonenal in the pathogenesis of leptin resistance in obesity.

Am J Physiol Cell Physiol 2019 May 21;316(5):C641-C648. Epub 2019 Feb 21.

Department of Pharmacotherapy, Graduate School of Biomedical & Health Sciences, Hiroshima University , Hiroshima , Japan.

Insensitivity to the antiobesity hormone, leptin, has been suggested to be involved in the pathogenesis of obesity. However, the pathological mechanisms underlying the development of leptin resistance are not well-understood. This study aimed to examine the pathological mechanisms of leptin resistance in obesity. Read More

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http://dx.doi.org/10.1152/ajpcell.00080.2018DOI Listing

The HECT ubiquitin E3 ligase Smurf2 degrades μ-opioid receptor 1 in the ubiquitin-proteasome system in lung epithelial cells.

Am J Physiol Cell Physiol 2019 May 13;316(5):C632-C640. Epub 2019 Feb 13.

Department of Physiology and Cell Biology, The Ohio State University , Columbus, Ohio.

Opioids are widely used for relieving clinical acute or chronic pain. The biological effects of opioids are through activating μ-opioid receptor 1 (MOR1). Most studies have focused on the consequences of agonist-induced MOR1 phosphorylation, ubiquitination, and internalization. Read More

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http://dx.doi.org/10.1152/ajpcell.00443.2018DOI Listing
May 2019
2 Reads

STF-62247 accumulates in lysosomes and blocks late stages of autophagy to selectively target von Hippel-Lindau-inactivated cells.

Am J Physiol Cell Physiol 2019 May 13;316(5):C605-C620. Epub 2019 Feb 13.

Department of Chemistry and Biochemistry, Université de Moncton , Moncton, New Brunswick , Canada.

Autophagy is a highly conserved, homeostatic process by which cytosolic components reach lysosomes for degradation. The roles played by different autophagic processes in cancer are complex and remain cancer type and stage dependent. Renal cell carcinoma (RCC) is the most common subtype of kidney cancer and is characterized by the inactivation of the von Hippel-Lindau (VHL) tumor suppressor. Read More

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http://dx.doi.org/10.1152/ajpcell.00483.2018DOI Listing
May 2019
1 Read

Dual-specificity phosphatase 4 is upregulated during skeletal muscle atrophy and modulates extracellular signal-regulated kinase activity.

Am J Physiol Cell Physiol 2019 Apr 13;316(4):C567-C581. Epub 2019 Feb 13.

Department of Biology, University of North Florida , Jacksonville, Florida.

Skeletal muscle atrophy results from disparate physiological conditions, including denervation, corticosteroid treatment, and aging. The purpose of this study was to describe and characterize the function of dual-specificity phosphatase 4 (Dusp4) in skeletal muscle after it was found to be induced in response to neurogenic atrophy. Quantitative PCR and Western blot analysis revealed that Dusp4 is expressed during myoblast proliferation but rapidly disappears as muscle cells differentiate. Read More

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http://dx.doi.org/10.1152/ajpcell.00234.2018DOI Listing
April 2019
1 Read

Posttranslational modifications of mitochondrial fission and fusion proteins in cardiac physiology and pathophysiology.

Am J Physiol Cell Physiol 2019 May 13;316(5):C583-C604. Epub 2019 Feb 13.

Lillehei Heart Institute, Cardiovascular Division, Department of Medicine, University of Minnesota , Minneapolis, Minnesota.

Mitochondrial fragmentation frequently occurs in chronic pathological conditions as seen in various human diseases. In fact, abnormal mitochondrial morphology and mitochondrial dysfunction are hallmarks of heart failure (HF) in both human patients and HF animal models. A link between mitochondrial fragmentation and cardiac pathologies has been widely proposed, but the physiological relevance of mitochondrial fission and fusion in the heart is still unclear. Read More

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http://dx.doi.org/10.1152/ajpcell.00523.2018DOI Listing
May 2019
1 Read

Polymerase-δ-interacting protein 2 activates the RhoGEF epithelial cell transforming sequence 2 in vascular smooth muscle cells.

Am J Physiol Cell Physiol 2019 May 6;316(5):C621-C631. Epub 2019 Feb 6.

Department of Medicine, Division of Cardiology, Emory University School of Medicine , Atlanta, Georgia.

Polymerase-δ-interacting protein 2 (Poldip2) controls a wide variety of cellular functions and vascular pathologies. To mediate these effects, Poldip2 interacts with numerous proteins and generates reactive oxygen species via the enzyme NADPH oxidase 4 (Nox4). We have previously shown that Poldip2 can activate the Rho family GTPase RhoA, another signaling node within the cell. Read More

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http://dx.doi.org/10.1152/ajpcell.00208.2018DOI Listing

Impact of real-time shedding on binding kinetics of membrane-remaining L-selectin to PSGL-1.

Am J Physiol Cell Physiol 2019 Feb 6. Epub 2019 Feb 6.

Center of Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences. School of Engineering Science, University of Chinese Academy of Sciences, China.

L-selectin shedding induced by various cytokines is crucial in activating neutrophils (PMNs) in inflammatory cascade. While the real-time shedding in vivo lasts about 10 min after PMN activation, the impact of time-dependent shedding on binding kinetics of membrane-remaining L-selectins to its ligands is poorly understood at transient or steady state. Here we developed an in vitro L-selectin shedding dynamics approach, together with competitive assays of cell adhesion, and proposed a theoretical model for quantifying the impact of real-time shedding on the binding kinetics of membrane-remaining L-selectins to PSGL-1. Read More

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http://dx.doi.org/10.1152/ajpcell.00212.2018DOI Listing
February 2019
6 Reads

MicroRNA-135a participates in the development of astrocytes derived from bacterial meningitis by downregulating HIF-1α.

Am J Physiol Cell Physiol 2019 Feb 6. Epub 2019 Feb 6.

Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Accumulating evidence has highlighting the potential of microRNAs (miRs) as biomarkers in various human diseases. However, the roles of miRs in bacterial meningitis (BM), a severe infectious condition, still remain unclear. Thus, the present study aimed to investigate the effects of miR-135a on proliferation and apoptosis of astrocytes in BM. Read More

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http://dx.doi.org/10.1152/ajpcell.00440.2018DOI Listing
February 2019
7 Reads

Spatially selective myosin regulatory light chain regulation is absent in dedifferentiated vascular smooth muscle cells but is partially induced by fibronectin and Klf4.

Am J Physiol Cell Physiol 2019 Apr 30;316(4):C509-C521. Epub 2019 Jan 30.

Division of Bioengineering, Graduate School of Engineering Science, Osaka University , Osaka , Japan.

The phosphorylation state of myosin regulatory light chain (MRLC) is central to the regulation of contractility that impacts cellular homeostasis and fate decisions. Rho-kinase (ROCK) and myosin light chain kinase (MLCK) are major kinases for MRLC documented to selectively regulate MRLC in a subcellular position-specific manner; specifically, MLCK in some nonmuscle cell types works in the cell periphery to promote migration, while ROCK does so at the central region to sustain contractility. However, it remains unclear whether or not the spatially selective regulation of the MRLC kinases is universally present in other cell types, including dedifferentiated vascular smooth muscle cells (SMCs). Read More

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http://dx.doi.org/10.1152/ajpcell.00251.2017DOI Listing

ANXA4 promotes trophoblast invasion via the PI3K/Akt/eNOS pathway in preeclampsia.

Am J Physiol Cell Physiol 2019 Apr 23;316(4):C481-C491. Epub 2019 Jan 23.

Department of Obstetrics and Gynecology, Peking University People's Hospital , Beijing , China.

The inadequate trophoblast invasion is associated with the development of preeclampsia (PE). Considering that annexin A4 (ANXA4) enhances tumor invasion, we aimed to explore the functional role of ANXA4 in trophoblast cells and to examine the underlying mechanism. ANXA4 expression in PE placentas was analyzed using immunohistochemistry and Western blotting. Read More

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https://www.physiology.org/doi/10.1152/ajpcell.00404.2018
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http://dx.doi.org/10.1152/ajpcell.00404.2018DOI Listing
April 2019
10 Reads

miR-222 represses expression of zipcode binding protein-1 and phospholipase C-γ1 in intestinal epithelial cells.

Am J Physiol Cell Physiol 2019 Mar 16;316(3):C415-C423. Epub 2019 Jan 16.

Cell Biology Group, Department of Surgery, University of Maryland School of Medicine , Baltimore, Maryland.

Both zipcode binding protein-1 (ZBP1) and phospholipase C-γ1 (PLCγ1) are intimately involved in many aspects of early intestinal mucosal repair after acute injury, but the exact mechanisms that control their cellular abundances remain largely unknown. The present study shows that microRNA-222 (miR-222) interacts with the mRNAs encoding ZBP1 and PLCγ1 and regulates ZBP1 and PLCγ1 expression in intestinal epithelial cells (IECs). The biotinylated miR-222 bound specifically to the ZBP1 and PLCγ1 mRNAs in IECs. Read More

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https://www.physiology.org/doi/10.1152/ajpcell.00165.2018
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http://dx.doi.org/10.1152/ajpcell.00165.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457099PMC
March 2019
6 Reads

A physiological drop in pH decreases mitochondrial respiration, and HDAC and Akt signaling, in L6 myocytes.

Am J Physiol Cell Physiol 2019 Mar 16;316(3):C404-C414. Epub 2019 Jan 16.

Institute for Health and Sport, Victoria University , Melbourne, Victoria , Australia.

Exercise stimulates mitochondrial biogenesis and increases mitochondrial respiratory function and content. However, during high-intensity exercise muscle pH can decrease below pH 6.8 with a concomitant increase in lactate concentration. Read More

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http://dx.doi.org/10.1152/ajpcell.00214.2018DOI Listing

TRPV2 channels mediate insulin secretion induced by cell swelling in mouse pancreatic β-cells.

Am J Physiol Cell Physiol 2019 Mar 16;316(3):C434-C443. Epub 2019 Jan 16.

Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka City, Japan.

β-Cell swelling induces membrane depolarization, which has been suggested to be caused at least partly by the activation of cation channels. Here, we show the identification of the cation channels. In isolated mouse pancreatic β-cells, the exposure to 30% hypotonic solution elicited an increase in cytosolic Ca concentration ([Ca]). Read More

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http://dx.doi.org/10.1152/ajpcell.00210.2017DOI Listing

Kinetic studies of K-Cl cotransport in cultured rat vascular smooth muscle cells.

Am J Physiol Cell Physiol 2019 Feb 16;316(2):C274-C284. Epub 2019 Jan 16.

The Cell Biophysics Group, Wright State University , Dayton, Ohio.

During aging, and development of atherosclerosis and cardiovascular disease (CVD), aortic vascular smooth muscle cells (VSMCs) transition from healthy contractile to diseased synthetic phenotypes. K-Cl cotransport (KCC) maintains cell volume and ion homeostasis in growth and differentiation, and hence is important for VSMC proliferation and migration. Therefore, KCC activity may play a role in the contractile-to-synthetic VSMC phenotypic transition. Read More

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http://dx.doi.org/10.1152/ajpcell.00002.2017DOI Listing
February 2019
6 Reads

Exercise training impacts skeletal muscle gene expression related to the kynurenine pathway.

Am J Physiol Cell Physiol 2019 Mar 16;316(3):C444-C448. Epub 2019 Jan 16.

Department of Kinesiology, McMaster University , Hamilton, Ontario , Canada.

Exercise positively impacts mood and symptoms of depression; however, the mechanisms underlying these effects are not fully understood. Recent evidence highlights a potential role for skeletal muscle-derived transcription factors to influence tryptophan metabolism, along the kynurenine pathway, which has important implications in depression. This has important consequences for older adults, whose age-related muscle deterioration may influence this pathway and may increase their risk for depression. Read More

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https://www.physiology.org/doi/10.1152/ajpcell.00448.2018
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http://dx.doi.org/10.1152/ajpcell.00448.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457098PMC
March 2019
6 Reads

α T-type calcium channel determines the angiogenic potential of pulmonary microvascular endothelial cells.

Am J Physiol Cell Physiol 2019 Mar 16;316(3):C353-C364. Epub 2019 Jan 16.

Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham , Birmingham, Alabama.

Pulmonary microvascular endothelial cells (PMVECs) display a rapid angioproliferative phenotype, essential for maintaining homeostasis in steady-state and promoting vascular repair after injury. Although it has long been established that endothelial cytosolic Ca ([Ca]) transients are required for proliferation and angiogenesis, mechanisms underlying such regulation and the transmembrane channels mediating the relevant [Ca] transients remain incompletely understood. In the present study, the functional role of the microvascular endothelial site-specific α T-type Ca channel in angiogenesis was examined. Read More

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http://dx.doi.org/10.1152/ajpcell.00336.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457103PMC
March 2019
3.780 Impact Factor

Smooth muscle cell-specific knockout of neuropilin-1 impairs postnatal lung development and pathological vascular smooth muscle cell accumulation.

Am J Physiol Cell Physiol 2019 Mar 16;316(3):C424-C433. Epub 2019 Jan 16.

Centre for Cardiovascular Biology and Medicine, BHF Laboratories, Division of Medicine, University College London , London , United Kingdom.

Neuropilin 1 (NRP1) is important for neuronal and cardiovascular development due to its role in conveying class 3 semaphorin and vascular endothelial growth factor signaling, respectively. NRP1 is expressed in smooth muscle cells (SMCs) and mediates their migration and proliferation in cell culture and is implicated in pathological SMC remodeling in vivo. To address the importance of Nrp1 for SMC function during development, we generated conditional inducible Nrp1 SMC-specific knockout mice. Read More

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http://dx.doi.org/10.1152/ajpcell.00405.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457104PMC
March 2019
1 Read