9,386 results match your criteria phosphorylation mtor

Pyraclostrobin induced AMPK/mTOR pathways mediated autophagy in RAW264.7 macrophages.

J Environ Sci Health B 2021 Aug 4:1-8. Epub 2021 Aug 4.

Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, China.

Pyraclostrobin(PCT) is a highly effective and broad-spectrum strobilurin fungicide. The mode action of PCT is inhibiting mitochondrial respiration. With the widespread use of PCT in preventing and controlling crop diseases, its potential safety risks to mammals have gradually attracted attention. Read More

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mTORC2-mediated direct phosphorylation regulates YAP activity promoting glioblastoma growth and invasive characteristics.

Neoplasia 2021 Jul 31;23(9):951-965. Epub 2021 Jul 31.

Departments of Medicine; Jonnson Comprehensive Cancer Center; Molecular Biology Institute, University of California-Los Angeles, CL; Department of Research & Development, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, CL. Electronic address:

The Hippo and mTOR signaling cascades are major regulators of cell growth and division. Aberrant regulation of these pathways has been demonstrated to contribute to gliomagenesis and result in enhanced glioblastoma proliferation and invasive characteristics. Several crosstalk mechanisms have been described between these two pathways, although a complete picture of these signaling interactions is lacking and is required for effective therapeutic targeting. Read More

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Autophagy is required for the promoting effect of angiogenic factor with G patch domain and forkhead-associated domain 1 (AGGF1) in retinal angiogenesis.

Microvasc Res 2021 Jul 30:104230. Epub 2021 Jul 30.

Department of Endocrinology, The First Affiliated Hospital of Xi'an Medical University, No.48 West Fenghao Road, Xi'an, 710077, Shaanxi, China.

Objective: To investigate the effect of angiogenic factor with G patch domain and forkhead-associated domain 1 (AGGF1) on retinal angiogenesis in ischemic retinopathy and its association with autophagy.

Methods: RF/6A cells were divided into the control group, hypoxia group and high-glucose group, and the expression of AGGF1 in cells was detected. C57BL/6 J mice were divided into the control group, oxygen-induced retinopathy (OIR) group and diabetic retinopathy (DR) group, and AGGF1 expression in the retina was observed. Read More

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2,6-Dimethoxy-1,4-benzoquinone increases skeletal muscle mass and performance by regulating AKT/mTOR signaling and mitochondrial function.

Phytomedicine 2021 Jul 10;91:153658. Epub 2021 Jul 10.

Division of Food Functionality Research, Korea Food Research Institute, Wanju-gun 55365, South Korea; Division of Food Biotechnology, University of Science and Technology, Daejeon 34113, South Korea. Electronic address:

Background: 2,6-Dimethoxy-1,4-benzoquinone (DMBQ), a natural phytochemical present in fermented wheat germ, has been reported to exert anti-cancer, anti-inflammatory, and anti-adipogenic effects. However, the effect of DMBQ on muscle hypertrophy and myoblast differentiation has not been elucidated.

Purpose: We investigated the effect of DMBQ on skeletal muscle mass and muscle function and then determined the possible mechanism of DMBQ. Read More

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The PI3K/mTOR Inhibitor Ompalisib Suppresses Nonhomologous End Joining and Sensitizes Cancer Cells to Radio- and Chemotherapy.

Mol Cancer Res 2021 Jul 30. Epub 2021 Jul 30.

Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University

As the predominant pathway for the repair of DNA double-strand breaks (DSBs), non-homologous end joining (NHEJ) attenuates the efficacy of cancer treatment which relies on the introduction of DSBs, such as radiotherapy and genotoxic drugs. Identifying novel NHEJ inhibitors is of great importance for improving the therapeutic efficiency of radio- or chemotherapy. Here we miniaturized our recently developed NHEJ detecting system into a 96-well plate-based format and interrogated an FDA approved drug library containing 1732 compounds. Read More

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Targeting cap-dependent translation to inhibit Chikungunya virus replication: selectivity of p38 MAPK inhibitors to virus-infected cells due to autophagy-mediated down regulation of phospho-ERK.

J Gen Virol 2021 Jul;102(7)

Molecular Virology Laboratory, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram 695014, Kerala, India.

The 5' capped, message-sense RNA genome of Chikungunya virus (CHIKV) utilizes the host cell machinery for translation. Translation is regulated by eIF2 alpha at the initiation phase and by eIF4F at cap recognition. Translational suppression by eIF2 alpha phosphorylation occurs as an early event in many alphavirus infections. Read More

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MyD88-mediated signaling intercedes in neurogenic muscle atrophy through multiple mechanisms.

FASEB J 2021 08;35(8):e21821

Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, TX, USA.

Skeletal muscle atrophy is a debilitating complication of many chronic disease states and disuse conditions including denervation. However, molecular and signaling mechanisms of muscle wasting remain less understood. Here, we demonstrate that the levels of several toll-like receptors (TLRs) and their downstream signaling adaptor, myeloid differentiation primary response 88 (MyD88), are induced in skeletal muscle of mice in response to sciatic nerve denervation. Read More

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Mechanical Overloading Induced-Activation of mTOR Signaling in Tendon Stem/Progenitor Cells Contributes to Tendinopathy Development.

Front Cell Dev Biol 2021 12;9:687856. Epub 2021 Jul 12.

MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, United States.

Despite the importance of mechanical loading in tendon homeostasis and pathophysiology, the molecular responses involved in the mechanotransduction in tendon cells remain unclear. In this study, we found that mechanical loading activated the mammalian target of rapamycin (mTOR) in rat patellar tendon stem/progenitor cells (TSCs) in a stretching magnitude-dependent manner. Application of rapamycin, a specific inhibitor of mTOR, attenuated the phosphorylation of S6 and 4E-BP1 and as such, largely inhibited the mechanical activation of mTOR. Read More

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Hepatotoxic Effect of Tramadol and O-desmethyltramadol in HepG2 cells and Potential role of PI3K/AKT/mTOR.

Xenobiotica 2021 Jul 28:1-23. Epub 2021 Jul 28.

Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Mansoura University , Egypt.

The aim of this study was to compare the in vitro cytotoxic effect of tramadol and M1 metabolite in HepG2 cell line, the underlying mechanism, and PI3K/AKT/mTOR as potential target. Concentrations representing therapeutic level for tramadol (2 µM) and M1 metabolite (0.5 µM) were used. Read More

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Protein phosphatase 6 promotes neurite outgrowth by promoting mTORC2 activity in N2a cells.

J Biochem 2021 Jul 26. Epub 2021 Jul 26.

Laboratory of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, 753-8515, Japan.

Understanding the molecular mechanism of neuronal differentiation is important to overcome the incurable diseases caused by nervous system damage. Neurite outgrowth is prerequisite for neuronal differentiation and regeneration, and cAMP response element-binding protein (CREB) is one of the major transcriptional factors positively regulating this process. Neuronal differentiation stimuli activate mammalian target of rapamycin (mTOR) complex 2 (mTORC2)/Akt signaling to phosphorylate CREB, however, the precise molecular mechanism of this event has not been fully understood. Read More

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Chronic Exercise Protects against the Progression of Renal Cyst Growth and Dysfunction in Rats with Polycystic Kidney Disease.

Med Sci Sports Exerc 2021 Jul 21. Epub 2021 Jul 21.

Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Sendai, Japan Division of General Medicine and Rehabilitation, Tohoku Medical and Pharmaceutical University Faculty of Medicine, Sendai, Japan.

Introduction: Polycystic kidney disease (PKD) is a genetic disorder characterized by the progressive enlargement of renal epithelial cysts and renal dysfunction. Previous studies have reported the beneficial effects of chronic exercise on chronic kidney disease. However, the effects of chronic exercise have not been fully examined in PKD patients or models. Read More

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Quercetin protects oral mucosal keratinocytes against lipopolysaccharide-induced inflammatory toxicity by suppressing the AKT/AMPK/mTOR pathway.

Immunopharmacol Immunotoxicol 2021 Jul 26:1-8. Epub 2021 Jul 26.

Department of Pharmacy, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China.

Background: Cytokines can induce a chronic inflammatory response in the periodontium, leading to periodontitis. Quercetin, a naturally occuring flavonoid, has been shown to inhibit periodontitis, but how it works is poorly understood. In this study, we assessed the impact of quercetin on lipopolysaccharide (LPS)-induced inflammatory damage in oral mucosal keratinocytes (hOMK107) and explored its underlying mechanism. Read More

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Biochanin A Inhibits Glioblastoma Growth Restricting Glycolysis and Mitochondrial Oxidative Phosphorylation.

Front Oncol 2021 8;11:652008. Epub 2021 Jul 8.

Department of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, China.

Abnormal metabolism serves a critical role in glioblastoma (GBM). Biochanin A (BCA), a flavonoid phenolic compound found in edible and herbal plants, has antioxidative and antitumor activities. However, it remains unclear whether BCA has an effect on energy metabolism. Read More

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Allosteric Modulation of GSK-3β as a New Therapeutic Approach in Limb Girdle Muscular Dystrophy R1 Calpain 3-Related.

Int J Mol Sci 2021 Jul 8;22(14). Epub 2021 Jul 8.

Biodonostia Health Research Institute, Neurosciences Area, 20014 San Sebastian, Spain.

Limb-girdle muscular dystrophy R1 calpain 3-related (LGMDR1) is an autosomal recessive muscular dystrophy produced by mutations in the gene. It is a rare disease and there is no cure or treatment for the disease while the pathophysiological mechanism by which the absence of calpain 3 provokes the dystrophy in muscles is not clear. However, key proteins implicated in Wnt and mTOR signaling pathways, which regulate muscle homeostasis, showed a considerable reduction in their expression and in their phosphorylation in LGMDR1 patients' muscles. Read More

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Deregulation of Exo70 Facilitates Innate and Acquired Cisplatin Resistance in Epithelial Ovarian Cancer by Promoting Cisplatin Efflux.

Cancers (Basel) 2021 Jul 11;13(14). Epub 2021 Jul 11.

Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, China.

Whilst researches elucidating a diversity of intracellular mechanisms, platinum-resistant epithelial ovarian cancer (EOC) remains a major challenge in the treatment of ovarian cancer. Here we report that Exo70, a key subunit of the exocyst complex, contributes to both innate and acquired cisplatin resistance of EOC. Upregulation of Exo70 is observed in EOC tissues and is related to platinum resistance and progression-free survival of EOC patients. Read More

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Selenium attenuates ischemia/reperfusion injury‑induced damage to the blood‑brain barrier in hyperglycemia through PI3K/AKT/mTOR pathway‑mediated autophagy inhibition.

Int J Mol Med 2021 Sep 23;48(3). Epub 2021 Jul 23.

Ningxia Key Laboratory of Cerebrocranial Diseases, School of Basic Medical Science, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China.

Ischemic stroke is a leading cause of mortality and disability. Diabetes mellitus, characterized by hyperglycemia, is a common concomitant disease of ischemic stroke, which is associated with autophagy dysfunction and blood‑brain barrier (BBB) damage following cerebral ischemia/reperfusion (I/R) injury. At present, there is no effective treatment strategy for the disease. Read More

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September 2021

mTORC1 Signaling Regulates Proinflammatory Macrophage Function and Metabolism.

J Immunol 2021 08 21;207(3):913-922. Epub 2021 Jul 21.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD;

Metabolic programming is integrally linked to immune cell function. Nowhere is this clearer than in the differentiation of macrophages. Proinflammatory M1 macrophages primarily use glycolysis as a rapid energy source but also to generate antimicrobial compounds, whereas alternatively activated M2 macrophages primarily rely on oxidative phosphorylation for the longevity required for proper wound healing. Read More

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Neuronal activity-induced SUMOylation of Akt1 by PIAS3 is required for long-term potentiation of synaptic transmission.

FASEB J 2021 08;35(8):e21769

Jiangsu Key Laboratory of Brain Disease Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Xuzhou, China.

Neuronal activity regulates spatial distribution of the SUMOylation system in cytosolic and dendritic sites, which has been implicated in learning, memory, and underlying synaptic structural and functional remodeling in the hippocampus. However, the functional target proteins for activated small ubiquitin-like modifiers (SUMOs) and downstream molecular consequences behind long-term potentiation (LTP) of synaptic plasticity remain to be elucidated. In this study, we showed that N-methyl-D-aspartate receptor-mediated neuronal activity induced the covalent modification of cytosolic Akt1 by small ubiquitin-like modifier 1 (SUMO1) in rat cortical and hippocampal CA1 neurons. Read More

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PIN1 Protects Hair Cells and Auditory HEI-OC1 Cells against Senescence by Inhibiting the PI3K/Akt/mTOR Pathway.

Oxid Med Cell Longev 2021 2;2021:9980444. Epub 2021 Jun 2.

Department of Otorhinolaryngology, The Second Hospital of Hebei Medical University, No. 215 West Heping Road, Shijiazhuang 050000, China.

A growing amount of evidence has confirmed the crucial role of the prolyl isomerase PIN1 in aging and age-related diseases. However, the mechanism of PIN1 in age-related hearing loss (ARHL) remains unclear. Pathologically, ARHL is primarily due to the loss and dysfunction of hair cells (HCs) and spiral ganglion cells (SGCs) in the cochlea. Read More

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MRPL13 Act as a Novel Therapeutic Target and Could Promote Cell Proliferation in Non-Small Cell Lung Cancer.

Cancer Manag Res 2021 12;13:5535-5545. Epub 2021 Jul 12.

Department of Respiratory Medicine, Affiliated Hospital of Shandong University of Chinese Medicine, Jinan, People's Republic of China.

Background: The latent involvement of MRPL13 in non-small cell lung cancer (NSCLC) remains unclear. This study aimed to explore the role of MRPL13 in NSCLC.

Methods: All analyses were performed in R software 4. Read More

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Cetyltrimethylammonium Bromide Attenuates the Mesenchymal Characteristics of Hypopharyngeal Squamous Cell Carcinoma Through Inhibiting the EGFR/PI3K/AKT Signaling Pathway.

Anticancer Res 2021 Aug;41(8):3789-3799

Department of Medical Research, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan, R.O.C.

Background/aim: Cetyltrimethylammonium bromide (CTAB), a quaternary ammonium surfactant, was shown to have antitumor effects in a cellular mode of head and neck squamous cell carcinoma (HNSCC), modulating apoptotic and cytotoxic processes. However, the mechanisms by which CTAB exerts its effects against the epithelial- mesenchymal transition in HNSCC remain poorly understood. In the present study, we investigated whether CTAB inhibits cellular mobility and invasiveness of hypopharyngeal squamous cell carcinoma (HPSCC) cells. Read More

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Adenosine Induces Autophagy in Cholangiocarcinoma Cells.

Anticancer Res 2021 Aug;41(8):3769-3778

Laboratory of Pharmacology, Chulabhorn Research Institute, Bangkok, Thailand

Background/aim: Cholangiocarcinoma is a lethal disease with increasing incidence worldwide. New therapeutic compounds are urgently needed for this disease. Here, the inhibitory effect of adenosine on cholangiocarcinoma cells was studied. Read More

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Low-Dose Acrolein, an Endogenous and Exogenous Toxic Molecule, Inhibits Glucose Transport via an Inhibition of Akt-Regulated GLUT4 Signaling in Skeletal Muscle Cells.

Int J Mol Sci 2021 Jul 5;22(13). Epub 2021 Jul 5.

Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.

Urinary acrolein adduct levels have been reported to be increased in both habitual smokers and type-2 diabetic patients. The impairment of glucose transport in skeletal muscles is a major factor responsible for glucose uptake reduction in type-2 diabetic patients. The effect of acrolein on glucose metabolism in skeletal muscle remains unclear. Read More

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Tacrolimus inhibits insulin release and promotes apoptosis of Min6 cells through the inhibition of the PI3K/Akt/mTOR pathway.

Mol Med Rep 2021 Sep 19;24(3). Epub 2021 Jul 19.

Department of Clinical Pharmacy, General Hospital of Central Theater Command, Wuhan, Hubei 430000, P.R. China.

As a calcineurin inhibitor, tacrolimus is commonly used as a first‑line immunosuppressant in organ transplant recipients. Post‑transplantation diabetes mellitus (PTDM) is a common complication following kidney transplantation and is associated with immunosuppressant drugs, such as tacrolimus. PTDM caused by tacrolimus may be related to its influence on insulin secretion and insulin resistance. Read More

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September 2021

Asiaticoside reduces autophagy and improves memory in a rat model of dementia through mTOR signaling pathway regulation.

Mol Med Rep 2021 Sep 19;24(3). Epub 2021 Jul 19.

Department of Neurology, Dongying District People's Hospital of Dongying City, Dongying, Shandong 257000, P.R. China.

Vascular dementia (VD) is one of the leading causes of neurological disorder following Alzheimer's disease. The present study evaluated the possible role of asiaticoside in the treatment of rats with VD and its inhibitory effects on autophagy in hippocampal tissues. Double ligation was used for permanent occlusion of the arteries, and spatial memory was assessed using the T‑maze test. Read More

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September 2021

Bta-miR-34b controls milk fat biosynthesis via the Akt/mTOR signaling pathway by targeting RAI14 in bovine mammary epithelial cells.

J Anim Sci Biotechnol 2021 Jul 19;12(1):83. Epub 2021 Jul 19.

College of Animal Science and Technology, Northwest A&F University, Xianyang, 712100, Shaanxi, China.

Background: The biosynthesis of milk fat affects both the technological properties and organoleptic quality of milk and dairy products. MicroRNAs (miRNAs) are endogenous small non-coding RNAs that inhibit the expression of their mRNA targets and are involved in downstream signaling pathways that control several biological processes, including milk fat synthesis. miR-34b is a member of the miR-34 miRNA cluster, which is differentially expressed in the mammary gland tissue of dairy cows during lactation and dry periods. Read More

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Andrographolide alleviates bleomycin-induced NLRP3 inflammasome activation and epithelial-mesenchymal transition in lung epithelial cells by suppressing AKT/mTOR signaling pathway.

Ann Transl Med 2021 May;9(9):764

Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: Andrographolide (Andro), a diterpenoid extracted from , has been shown to attenuate pulmonary fibrosis in rodents; however, the potential mechanisms remain largely unclear. This study investigated whether and how Andro alleviates bleomycin (BLM)-induced NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and epithelial-mesenchymal transition (EMT) in the lung epithelial cells.

Methods: The effects of Andro were evaluated in a rat model of BLM-induced pulmonary fibrosis. Read More

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Bone morphogenetic protein-7 inhibits endothelial-to-mesenchymal transition in primary human umbilical vein endothelial cells and mouse model of systemic sclerosis via Akt/mTOR/p70S6K pathway.

J Dermatol Sci 2021 Jun 27. Epub 2021 Jun 27.

Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address:

Background: Systemic sclerosis (SSc) is an autoimmune inflammatory and vascular disorder that causes tissue fibrosis of the skin and internal organs. Endothelial-to-mesenchymal transition (EndoMT) has been considered an important mechanism in the pathogenesis of vascular remodeling in SSc. Recent studies suggested that bone morphogenic protein 7 (BMP-7) has anti-fibrotic effects in several fibrotic diseases. Read More

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B7-H3 on breast cancer cell MCF7 inhibits IFN-γ release from tumour-infiltrating T cells.

Pathol Res Pract 2021 May 5;224:153461. Epub 2021 May 5.

Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China. Electronic address:

B7-H3 is a type I membrane protein that has contradictory co-stimulatory and co-inhibitory effects in adaptive and anti-tumour immunity. B7-H3 is up-regulated in many malignant tumours, including breast cancer. Therefore, we hypothesise that B7-H3, which has an immunosuppressive role, suppresses anti-tumour immunity. Read More

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The Role of Ophiopogonin D in Atherosclerosis: Impact on Lipid Metabolism and Gut Microbiota.

Am J Chin Med 2021 14;49(6):1449-1471. Epub 2021 Jul 14.

The Fifth Affiliated Hospital, Southern Medical University, Guangzhou 510920, P. R. China.

Gut microbiota has been proven to play an important role in many metabolic diseases and cardiovascular disease, particularly atherosclerosis. Ophiopogonin D (OPD), one of the effective compounds in , is considered beneficial to metabolic syndrome and cardiovascular diseases. In this study, we have illuminated the effect of OPD in ApoE knockout (ApoE[Formula: see text] mice on the development of atherosclerosis and gut microbiota. Read More

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