48,183 results match your criteria mitochondrial dysfunction


Synthesis and evaluation of multi-target-directed ligands with BACE-1 inhibitory and Nrf2 agonist activities as potential agents against Alzheimer's disease.

Eur J Med Chem 2021 Apr 7;219:113441. Epub 2021 Apr 7.

Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address:

Cumulative evidence suggests that β-amyloid and oxidative stress are closely related with each other and play key roles in the process of Alzheimer's disease (AD). Multitarget regulation of both pathways might represent a promising therapeutic strategy. Here, a series of selenium-containing compounds based on ebselen and verubecestat were designed and synthesized. Read More

View Article and Full-Text PDF

Synthesis and in vivo screening of isosteviol derivatives as new cardioprotective agents.

Eur J Med Chem 2021 Mar 28;219:113396. Epub 2021 Mar 28.

School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, China. Electronic address:

Isosteviol, an ent-beyerane diterpenoid, has been repeatedly reported to possess potent cardioprotective activity. With the aim of discovering new cardioprotective derivatives from isosteviol, 47 compounds, including 40 new ones, were synthesized and evaluated in vivo using the easy-handling and efficient zebrafish model. The structure-activity relationship of this type of compounds was thus discussed. Read More

View Article and Full-Text PDF

A preliminary study on the mechanism of the neurosteroid-mediated ionotropic receptor dysfunction in neurodevelopmental toxicity induced by decabromodiphenyl ether.

Ecotoxicol Environ Saf 2021 Apr 13;217:112198. Epub 2021 Apr 13.

Department of Nutrition and Food Hygiene, Guilin Medical University, Guilin, Guangxi 541004, People's Republic of China; Guangxi Colleges and University Key Laboratory of Preventive Medicine, Guilin Medical University, Guilin, Guangxi 541004, People's Republic of China. Electronic address:

The mechanism of neurodevelopmental toxicity of decabromodiphenyl ether (BDE209) remains unclear. Recent evidence suggests that neurosteroids disorders play a vital role in BDE209 induced-neurodevelopmental toxicity. To explore the mechanism of it, pregnant ICR mice were orally gavaged with 0, 225, and 900 mg kg BDE209 for about 42 days. Read More

View Article and Full-Text PDF

Environmental pollutants exposure and male reproductive toxicity: the role of epigenetic modifications.

Toxicology 2021 Apr 13:152780. Epub 2021 Apr 13.

Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, China. Electronic address:

Male fertility rates have shown a progressive decrease in recent decades. There is a growing concern about the male reproductive dysfunction caused by environmental pollutants exposure, however the underlying molecular mechanisms are still not well understood. Epigenetic modifications play a key role in the biological responses to external stressors. Read More

View Article and Full-Text PDF

Manganese-induced alpha-synuclein overexpression aggravates mitochondrial damage by repressing PINK1/Parkin-mediated mitophagy.

Food Chem Toxicol 2021 Apr 13:112213. Epub 2021 Apr 13.

Department of Environmental Health, School of Public Health, China Medical University, Address: No.77 Puhe Road, Shenyang North New Area, Shenyang 110122, Liaoning, China. Electronic address:

Chronic manganese (Mn) exposure is related to elevated risks of neurodegenerative diseases, and mitochondrial dysfunction is considered a critical pathophysiological feature of Mn neurotoxicity. Although previous research has demonstrated Mn-induced alpha-synuclein (α-Syn) overexpression, the role of α-Syn in mitochondrial dysfunction remains unclear. Here, we used Wistar rats and human neuroblastoma cells (SH-SY5Y cells) to elucidate the molecular mechanisms underlying how α-Syn overexpression induced by different doses of Mn (15, 30, and 60 mg/kg) results in mitochondrial dysfunction. Read More

View Article and Full-Text PDF

S100B/RAGE/Ceramide signaling pathway is involved in sepsis-associated encephalopathy.

Life Sci 2021 Apr 13:119490. Epub 2021 Apr 13.

Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China. Electronic address:

Aims: Sepsis-associated encephalopathy (SAE) is one of the most common complications of sepsis, and it might lead to long-term cognitive dysfunction and disability. This study aimed to explore the role of S100 calcium binding protein B (S100B)/RAGE/ceramide signaling pathway in SAE.

Main Methods: FPS-ZM1 (an inhibitor of RAGE), myriocin and GW4869 (an inhibitor of ceramide) were used to explore the role of S100B/RAGE/ceramide in acute brain injury and long-term cognitive impairment in sepsis. Read More

View Article and Full-Text PDF

Hyperbaric oxygen therapy effectively alleviates D-galactose-induced-age-related cardiac dysfunction via attenuating mitochondrial dysfunction in pre-diabetic rats.

Aging (Albany NY) 2021 Apr 16;13. Epub 2021 Apr 16.

Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.

Currently, the prevalence of obesity in aging populations is fast growing worldwide. Aging induced by D-galactose (D-gal) is proven to cause the worsening of cardiac dysfunction in pre-diabetic rats via deteriorating cardiac mitochondrial function. Hyperbaric oxygen therapy (HBOT) has been shown to attenuate D-gal-induced cognitive deterioration through decreased inflammation and apoptosis. Read More

View Article and Full-Text PDF

Interorganelle communication, aging, and neurodegeneration.

Genes Dev 2021 Apr;35(7-8):449-469

Department of Physiology, University of California at San Francisco, San Francisco, California 94158, USA.

Our cells are comprised of billions of proteins, lipids, and other small molecules packed into their respective subcellular organelles, with the daunting task of maintaining cellular homeostasis over a lifetime. However, it is becoming increasingly evident that organelles do not act as autonomous discrete units but rather as interconnected hubs that engage in extensive communication through membrane contacts. In the last few years, our understanding of how these contacts coordinate organelle function has redefined our view of the cell. Read More

View Article and Full-Text PDF

Deficiency in Nebulin Repeats of Sarcomeric Nebulette is Detrimental for Cardiomyocyte Tolerance to Exercise and Biomechanical Stress.

Am J Physiol Heart Circ Physiol 2021 Apr 16. Epub 2021 Apr 16.

The Heart Institute, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN; Children's Foundation Research Institute, Le Bonheur Children's Hospital Memphis, TN, United States.

Background: The actin-binding sarcomeric nebulette (NEBL) protein provides efficient contractile flexibility via interaction with desmin intermediate filaments. NEBL gene mutations affecting the nebulin repeat (NR) domain is known to induce cardiomyopathy.

Objective: The study aimed to explore the roles of NEBL in exercise and biomechanical stress response. Read More

View Article and Full-Text PDF

Nanoemulsion Improves the Neuroprotective Effects of Curcumin in an Experimental Model of Parkinson's Disease.

Neurotox Res 2021 Apr 16. Epub 2021 Apr 16.

Programa de Pós-Graduação em Ciências da Saúde, Faculdade de Medicina, Campus Saúde, Universidade Federal do Rio Grande, Rua Visconde de Paranaguá, 102, Centro, Rio Grande, RS, 96203-900, Brazil.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor dysfunction. Recent studies have shown that curcumin (CUR) has neuroprotective effects in PD experimental models. However, its efficacy is limited due to low water solubility, bioavailability, and access to the central nervous system. Read More

View Article and Full-Text PDF

Pyruvate Dehydrogenase as a Therapeutic Target for Nonalcoholic Fatty Liver Disease.

ACS Pharmacol Transl Sci 2021 Apr 3;4(2):582-588. Epub 2021 Mar 3.

Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1, Canada.

Excess caloric intake combined with a sedentary lifestyle in the general population has greatly increased the prevalence of obesity and nonalcoholic fatty liver disease (NAFLD), which is defined as the accumulation of excess fat in the liver in the absence of alcohol abuse or other attributable causes such as infection with hepatitis C. Furthermore, NAFLD increases the risk for insulin resistance, type 2 diabetes (T2D), and cardiovascular disease, while currently having no approved therapy to counteract its pathology. Thus, increasing efforts to understand the mechanisms responsible for NAFLD have been pursued in preclinical studies, in the hopes of developing novel therapies that can prevent the progression of insulin resistance and/or T2D. Read More

View Article and Full-Text PDF

A Role of Glucose Overload in Diabetic Cardiomyopathy in Nonhuman Primates.

J Diabetes Res 2021 30;2021:9676754. Epub 2021 Mar 30.

Department of Cardiology, The Fourth Affiliated Hospital of China Medical University, Shenyang 110034, China.

Type 2 diabetes (T2D) plays a major role in the development of heart failure. Patients with T2D have an increased risk to develop HF than healthy subjects, and they always have very poor outcomes and survival rates. However, the underlying mechanisms for this are still unclear. Read More

View Article and Full-Text PDF

Update on the Mechanisms of Tubular Cell Injury in Diabetic Kidney Disease.

Front Med (Lausanne) 2021 30;8:661076. Epub 2021 Mar 30.

Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Increasing evidence supports a role of proximal tubular (PT) injury in the progression of diabetic kidney disease (DKD), in patients with or without proteinuria. Research on the mechanisms of the PT injury in DKD could help us to identify potential new biomarkers and drug targets for DKD. A high glucose transport state and mismatched local hypoxia in the PT of diabetes patients may be the initiating factors causing PT injury. Read More

View Article and Full-Text PDF

Impact of Mitochondrial Targeting Antibiotics on Mitochondrial Function and Proliferation of Cancer Cells.

ACS Med Chem Lett 2021 Apr 8;12(4):579-584. Epub 2021 Mar 8.

Novintum Biosciences Ltd, London Bioscience Innovation Centre, 2 Royal College Street, London, NW1 0NH, United Kingdom.

Some marketed antibiotics can cause mitochondria dysfunction via inhibition of the mitochondrial translation process. There is great interest in exploiting such effects within a cancer setting. To enhance accumulation of antibiotics within the mitochondria of cancer cells, and therefore delivery of a greater potency payload, a mitochondrial targeting group in the form of a triphenylphosphonium (TPP) cation was appended via an alkyl chain length consisting of 7 to 11 carbons to the ribosomal antibiotics azithromycin and doxycycline. Read More

View Article and Full-Text PDF

Bevacizumab-Induced Mitochondrial Dysfunction, Endoplasmic Reticulum Stress, and ERK Inactivation Contribute to Cardiotoxicity.

Oxid Med Cell Longev 2021 17;2021:5548130. Epub 2021 Mar 17.

Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Lung Cancer Center, Tianjin 300060, China.

The molecular mechanisms underlying the cardiotoxicity associated with bevacizumab, a first-line immunotherapeutic agent used to treat lung cancer, are not fully understood. Here, we examined intracellular signal transduction in cardiomyocytes after exposure to different doses of bevacizumab . Our results demonstrated that bevacizumab significantly and dose-dependently reduces cardiomyocyte viability and increases cell apoptosis. Read More

View Article and Full-Text PDF

Characterization of drug-induced human mitochondrial ADP/ATP carrier inhibition.

Theranostics 2021 5;11(11):5077-5091. Epub 2021 Mar 5.

Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Keith Peters Building, Hills Road, Cambridge, CB2 0XY, United Kingdom.

An increasing number of commonly prescribed drugs are known to interfere with mitochondrial function, causing cellular toxicity, but the underlying mechanisms are largely unknown. Although often not considered, mitochondrial transport proteins form a significant class of potential mitochondrial off-targets. So far, most drug interactions have been reported for the mitochondrial ADP/ATP carrier (AAC), which exchanges cytosolic ADP for mitochondrial ATP. Read More

View Article and Full-Text PDF

D-Chiro-Inositol Regulates Insulin Signaling in Human Adipocytes.

Front Endocrinol (Lausanne) 2021 30;12:660815. Epub 2021 Mar 30.

Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

D-Chiro-Inositol (D-Chiro-Ins) is a secondary messenger in the insulin signaling pathway. D-Chiro-Ins modulates insulin secretion, the mitochondrial respiratory chain, and glycogen storage. Due to these actions D-Chiro-Ins has been proposed to correct defective insulin function in a variety of conditions characterized by metabolic dysfunction, such as polycystic ovary syndrome (PCOS), obesity, gestational diabetes and fat accumulation at menopause. Read More

View Article and Full-Text PDF

Cannabidiol Induces Autophagy to Protects Neural Cells From Mitochondrial Dysfunction by Upregulating SIRT1 to Inhibits NF-κB and NOTCH Pathways.

Front Cell Neurosci 2021 30;15:654340. Epub 2021 Mar 30.

Medical School, Kunming University of Science and Technology, Kunming, China.

The protective effect of Cannabidiol on Parkinson's disease (PD) has been found in recent study. However, the specific mechanism of the protective effect of Cannabidiol on PD nerve damage require further exploration. This study aims to investigate effect of Cannabidiol on MMP-induced Neural Cells (SH-SY5Y) mitochondrial dysfunction. Read More

View Article and Full-Text PDF

Bioallethrin enhances generation of ROS, damages DNA, impairs the redox system and causes mitochondrial dysfunction in human lymphocytes.

Sci Rep 2021 Apr 15;11(1):8300. Epub 2021 Apr 15.

Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, UP, 202002, India.

Bioallethrin is a synthetic pesticide that is widely used to control insect pests. The wide use of bioallethrin has resulted in inevitable human exposure. In this study we report the effect of different concentrations of bioallethrin (10 to 200 µM, 2 h at 37 °C) on human lymphocytes under in vitro conditions. Read More

View Article and Full-Text PDF

Macrophages with reduced expressions of classical M1 and M2 surface markers in human bronchoalveolar lavage fluid exhibit pro-inflammatory gene signatures.

Sci Rep 2021 Apr 15;11(1):8282. Epub 2021 Apr 15.

St Paul's Hospital, The University of British Columbia (UBC) Centre for Heart Lung Innovation (HLI), Vancouver, BC, Canada.

The classical M1/M2 polarity of macrophages may not be applicable to inflammatory lung diseases including chronic obstructive pulmonary disease (COPD) due to the complex microenvironment in lungs and the plasticity of macrophages. We examined macrophage sub-phenotypes in bronchoalveolar lavage (BAL) fluid in 25 participants with CD40 (a M1 marker) and CD163 (a M2 marker). Of these, we performed RNA-sequencing on each subtype in 10 patients using the Illumina NextSeq 500. Read More

View Article and Full-Text PDF

Thymoquinone, extract from Nigella sativa seeds, protects human skin keratinocytes against UVA-irradiated oxidative stress, inflammation and mitochondrial dysfunction.

Mol Immunol 2021 Apr 12;135:21-27. Epub 2021 Apr 12.

Department of Traditional Chinese Medicine Pain Area of Orthopedic, Honghui Hospital, Xi'an Jiaotong University, Xianyang, Shaanxi 710064, China. Electronic address:

Ultraviolet A (UVA) irradiation caused skin keratinocytes to accumulate reactive oxygen species (ROS) leading to the skin injury. Thymoquinone (TQ) was identified as the prominent bioactive ingredient in Nigella sativa seeds which was applied in therapying various human diseases. This study aimed to illustrate the role and mechanism of TQ in UVA-induced skin injury. Read More

View Article and Full-Text PDF

Sarcoplasmic reticulum-mitochondria communication; implications for cardiac arrhythmia.

J Mol Cell Cardiol 2021 Apr 12. Epub 2021 Apr 12.

Department of Physiology and Cell Biology, Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH, United States of America. Electronic address:

Sudden cardiac death due to ventricular tachyarrhythmias remains the major cause of mortality in the world. Heart failure, diabetic cardiomyopathy, old age-related cardiac dysfunction and inherited disorders are associated with enhanced propensity to malignant cardiac arrhythmias. Both defective mitochondrial function and abnormal intracellular Ca homeostasis have been established as the key contributing factors in the pathophysiology and arrhythmogenesis in these conditions. Read More

View Article and Full-Text PDF

Neuromedin U uses Gαi2 and Gαo to suppress glucose-stimulated Ca2+ signaling and insulin secretion in pancreatic β cells.

PLoS One 2021 15;16(4):e0250232. Epub 2021 Apr 15.

Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.

Neuromedin U (NMU), a highly conserved peptide in mammals, is involved in a wide variety of physiological processes, including impairment of pancreatic β-cell function via induction of mitochondrial dysfunction and endoplasmic reticulum (ER) stress, ultimately suppressing insulin secretion. NMU has two receptors, NMU receptor 1 (NMUR1) and NMUR2, both of which are G-protein-coupled receptors (GPCRs). Only NMUR1 is expressed in mouse islets and β cell-derived MIN6-K8 cells. Read More

View Article and Full-Text PDF

Moschamindole induces glioma cell apoptosis by blocking Mia40-dependent mitochondrial intermembrane space assembly and oxidative respiration.

Phytother Res 2021 Apr 15. Epub 2021 Apr 15.

Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.

Glioblastoma multiforme (GBM) is the most frequent, lethal, and aggressive tumor of the central nervous system in adults. In this study, we found for the first time that moschamindole (MCD), a rare phenolic amide with 8/6/6/5/5 rings, is a major bioactive constituent derived from Phragmites communis Trin (Poaceae) that exhibits a potential cytotoxic effect on both TMZ-resistant GBM cell lines and xenograft models. MCD-induced intrinsic apoptosis signals and mitochondrial dysfunction were confirmed by cell cycle arrest, caspase-3/7 activation, and membrane potential depolarization. Read More

View Article and Full-Text PDF

Mitochondria-DNA copy-number and incident venous thromboembolism among middle-aged women: a population-based cohort study.

J Thromb Thrombolysis 2021 Apr 15. Epub 2021 Apr 15.

Center for Primary Health Care Research, Lund University/Region Skåne, Skåne University Hospital Malmö, University Hospital, Jan Waldenströms gata 35, SE-205 02, Malmö, Sweden.

Venous thromboembolism (VTE) is the third most common cardiovascular disease. Low amount of mitochondrial DNA copy number (mtDNA-CN) has been associated with arterial cardiovascular disease (CVD) and reflects mitochondrial dysfunctions. However, whether mtDNA-CN is associated with VTE has not been determined. Read More

View Article and Full-Text PDF

Hydrogen sulfide prevents ethanol-induced ZO-1 CpG promoter hypermethylation-dependent vascular permeability via miR-218/DNMT3a axis.

J Cell Physiol 2021 Apr 14. Epub 2021 Apr 14.

Department of Physiology, School of Medicine, University of Louisville, Louisville, Kentucky, USA.

Ethanol (ET) causes cerebrovascular dysfunction by altering homocysteine (Hcy) metabolism and by causing oxidative stress. However, there are no strategies to prevent ET-induced epigenetic deregulation of tight junction protein (hyper-methylation) and endothelial cell permeability to date. Hydrogen sulfide (H S) has an antioxidative, antiapoptotic, and anti-inflammatory effect. Read More

View Article and Full-Text PDF

Biallelic variants in LIG3 cause a novel mitochondrial neurogastrointestinal encephalomyopathy.

Brain 2021 Apr 15. Epub 2021 Apr 15.

Department of Morphology, Surgery and Experimental Medicine, St. Anna Hospital, University of Ferrara, Ferrara, 44124, Italy.

Abnormal gut motility is a feature of several mitochondrial encephalomyopathies, and mutations in genes such as TYMP and POLG, have been linked to these rare diseases. The human genome encodes three DNA ligases, of which only one, ligase III (LIG3), has a mitochondrial splice variant and is crucial for mitochondrial health. We investigated the effect of reduced LIG3 activity and resulting mitochondrial dysfunction in seven patients from three independent families, who showed the common occurrence of gut dysmotility and neurological manifestations reminiscent of mitochondrial neurogastrointestinal encephalomyopathy. Read More

View Article and Full-Text PDF

RIPK3 Induces Cardiomyocyte Necroptosis via Inhibition of AMPK-Parkin-Mitophagy in Cardiac Remodelling after Myocardial Infarction.

Oxid Med Cell Longev 2021 27;2021:6635955. Epub 2021 Mar 27.

Department of Respiratory and Critical Care Medicine, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China.

Receptor-interacting protein 3- (RIPK3-) modulated necroptosis plays a critical role in cardiac remodelling after myocardial infarction (MI). However, the precise regulatory mechanism is not fully elucidated yet. In the present study, we showed that RIPK3 expression was upregulated in myocardial tissue after MI in a mouse model by coronary artery ligation, as well as in the cardiomyocytes following hypoxic injury . Read More

View Article and Full-Text PDF

AIF3 splicing switch triggers neurodegeneration.

Mol Neurodegener 2021 Apr 14;16(1):25. Epub 2021 Apr 14.

Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

Background: Apoptosis-inducing factor (AIF), as a mitochondrial flavoprotein, plays a fundamental role in mitochondrial bioenergetics that is critical for cell survival and also mediates caspase-independent cell death once it is released from mitochondria and translocated to the nucleus under ischemic stroke or neurodegenerative diseases. Although alternative splicing regulation of AIF has been implicated, it remains unknown which AIF splicing isoform will be induced under pathological conditions and how it impacts mitochondrial functions and neurodegeneration in adult brain.

Methods: AIF splicing induction in brain was determined by multiple approaches including 5' RACE, Sanger sequencing, splicing-specific PCR assay and bottom-up proteomic analysis. Read More

View Article and Full-Text PDF

Oxygen Pathway Limitations in Patients with Chronic Thromboembolic Pulmonary Hypertension.

Circulation 2021 Apr 15. Epub 2021 Apr 15.

Baker Heart and Diabetes Institute, Melbourne, Australia; Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium; University Hospitals Leuven, Leuven, Belgium.

Exertional intolerance is a limiting and often crippling symptom in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Traditionally the etiology has been attributed to central factors, including ventilation-perfusion mismatch, increased pulmonary vascular resistance and right heart dysfunction and uncoupling. Pulmonary endarterectomy and, balloon pulmonary angioplasty provide substantial improvement of functional status and hemodynamics. Read More

View Article and Full-Text PDF