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X Zhang, Y Bu, B Zhu, Q Zhao, Z Lv, B Li, J Liu
Objectives: The aim of this study was to identify key pathological genes in osteoarthritis (OA). Methods: We searched and downloaded mRNA expression data from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) of joint synovial tissues from OA and normal individuals. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses were used to assess the function of identified DEGs. The protein-protein interaction (PPI) network and transcriptional factors (TFs) regulatory network were used to further explore the function of identified DEGs...
April 2018: Bone & Joint Research
Hai-Yin Li, Xian-Wu Lin, Shao-Lei Geng, Wei-Hua Xu
The transforming growth factor-β (TGF-β) superfamily signaling pathway contains two general branches, known as TGF-β and bone morphogenetic protein (BMP), that regulate development in animals. It is well known that TGF-β superfamily signaling participates in the regulation of dauer (lifespan extension) in Caenorhabditis elegans, but little is known about the molecular mechanisms of lifespan extension in the pathway. Diapause, a programmed developmental arrest in insects, is similar to dauer in C. elegans...
June 11, 2018: Biochimica et Biophysica Acta
Graeme A King, Maryam Hashemi Shabestari, Kees-Karel H Taris, Ashutosh K Pandey, Sundararajan Venkatesh, Jayapalraja Thilagavathi, Kamalendra Singh, Rama Krishna Koppisetti, Dmitry Temiakov, Wouter H Roos, Carolyn K Suzuki, Gijs J L Wuite
Mitochondrial transcription factor A (TFAM) is essential for the maintenance, expression and transmission of mitochondrial DNA (mtDNA). However, mechanisms for the post-translational regulation of TFAM are poorly understood. Here, we show that TFAM is lysine acetylated within its high-mobility-group box 1, a domain that can also be serine phosphorylated. Using bulk and single-molecule methods, we demonstrate that site-specific phosphoserine and acetyl-lysine mimics of human TFAM regulate its interaction with non-specific DNA through distinct kinetic pathways...
April 20, 2018: Nucleic Acids Research
Hung-Wen Liu, Sue-Joan Chang
The clear mechanism of moderate exercise training (Ex) in attenuating muscle loss remains elusive in diabetes. We investigated the effects of moderate exercise training on diabetes-induced nuclear factor-κB (NF-κB) activation and mitochondrial dysfunction. Skeletal muscle size and atrophy signaling pathways were examined in type 2 diabetic db/db mice with or without moderate exercise training (5.2 m/min, 1 h/day, and 5 days/week for a total of 8 weeks). Exercise training decreased serum leptin, MCP-1, and resistin levels in db/db +Ex mice, but it did not reduce symptoms of insulin resistance including hyperglycemia, hyperinsulinemia, and impaired glucose tolerance...
2018: Frontiers in Physiology
Xi Zhang, Yifan Feng, Yuping Wang, Jing Wang, Danni Xiang, Weiran Niu, Fei Yuan
AIMS: To explore the roles of mitochondrial biogenesis and dynamics in both RGC-5 cells apoptosis and rat retinal damage induced by elevated pressure and their involvement in resveratrol (RSV)-induced cell protection. MATERIALS AND METHODS: The chronic ocular hypertension (COH) model was established in rats by injecting superparamagnetic iron oxide into anterior chamber. The RGC-5 cells were incubated under ambient and elevated pressure (70 mm Hg) respectively...
June 9, 2018: Life Sciences
Dongshi Liang, Airong Huang, Yimei Jin, Miaomiao Lin, Xiaojiao Xia, Xiaoli Chen, Airong Huang
This study aimed to examine whether exogenous NaHS can protect myocardial mitochondrial injury from sepsis by enhancing the peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α)/ nuclear factor erythroid-2-related factor 2 (NRF2) pathway and mitochondrial biosynthesis in mice. Animals were divided into sham-operated, sepsis, sepsis + 25 μmol/L NaHS, sepsis + 50 μmol/L NaHS, sepsis + 100 μmol/L NaHS, and sepsis + 200 μmol/L NaHS groups. The myocardial damage was evaluated by hematoxylin and eosin staining for myocardial microstructure and serum cardiac troponin I (cTnI) detection...
2018: American Journal of Translational Research
Jenn-Haung Lai, Mei-Yi Wang, Chuan-Yueh Huang, Chien-Hsiang Wu, Li-Feng Hung, Chia-Ying Yang, Po-Yuan Ke, Shue-Fen Luo, Shih-Jen Liu, Ling-Jun Ho
Toll-like receptors (TLRs) are important sensors that recognize pathogen-associated molecular patterns. Generally, TLR9 is known to recognize bacterial or viral DNA but not viral RNA and initiate an immune response. Herein, we demonstrate that infection with dengue virus (DENV), an RNA virus, activates TLR9 in human dendritic cells (DCs). DENV infection induces release of mitochondrial DNA (mtDNA) into the cytosol and activates TLR9 signaling pathways, leading to production of interferons (IFNs). The DENV-induced mtDNA release involves reactive oxygen species generation and inflammasome activation...
June 7, 2018: EMBO Reports
Ying-Chu Chen, Yu-Hsiang Yu
Brown adipocyte lineage commitment and differentiation are under complex regulation. Brown adipocytes are derived from mesenchymal stem cells (MSCs). Whether porcine bone marrow-derived MSCs (BM-MSCs) possess the potential to differentiate into brown adipocytes remains unclear. In the current study, we evaluated the ability of porcine BM-MSCs to differentiate into brown adipocytes and browning of differentiated adipocytes. We found that similar to rodent models, bone morphogenetic protein 7 (BMP7) was able to trigger the commitment of BM-MSCs to the brown adipocyte lineage by elevating expression of marker genes, nrf-1, tfam, zic1 and pgc-1α (P < 0...
June 7, 2018: Journal of Animal Science
Minghua Yang, Changfeng Li, Shan Zhu, Lizhi Cao, Guido Kroemer, Herbert Zeh, Daolin Tang, Rui Kang
Immunogenic cell death (ICD) is a type of cell death that is accompanied by the release of damage-associated molecular patterns (DAMPs) and results in a dead-cell antigen-specific immune response. Here, we report that spautin-1, an inhibitor of ubiquitin-specific peptidases, triggers immunogenic cancer cell death in vitro and in vivo . The anticancer activity of spautin-1 occurs independent of autophagy inhibition, but depends on the intrinsic mitochondrial apoptosis pathway. Spautin-1 causes mitochondrial oxidative injury, which results in JUN transcription factor activation in a JNK-dependent manner...
2018: Oncoimmunology
Nicole M Chapman, Hu Zeng, Thanh-Long M Nguyen, Yanyan Wang, Peter Vogel, Yogesh Dhungana, Xiaojing Liu, Geoffrey Neale, Jason W Locasale, Hongbo Chi
Regulatory T (Treg ) cells derived from the thymus (tTreg ) and periphery (pTreg ) have central and distinct functions in immunosuppression, but mechanisms for the generation and activation of Treg subsets in vivo are unclear. Here, we show that mechanistic target of rapamycin (mTOR) unexpectedly supports the homeostasis and functional activation of tTreg and pTreg cells. mTOR signaling is crucial for programming activated Treg -cell function to protect immune tolerance and tissue homeostasis. Treg -specific deletion of mTOR drives spontaneous effector T-cell activation and inflammation in barrier tissues and is associated with reduction in both thymic-derived effector Treg (eTreg ) and pTreg cells...
May 29, 2018: Nature Communications
Rory P Cunningham, Mary P Moore, Grace M Meers, Gregory N Ruegsegger, Frank W Booth, R Scott Rector
INTRODUCTION: Maternal exercise and physical activity during the gestational period can be protective against maternal high fat diet-induced hepatic steatosis in older offspring. However, it is unknown whether these protective effects are seen in younger offspring. Here we investigated whether maternal physical activity would attenuate maternal western diet (WD)-induced steatosis in young adult rats. METHODS: Female Wistar rats (7-8 weeks of age) were randomized into WD (42% fat, 27% sucrose) or normal chow diet (ND), and further randomized into physical activity (RUN) or sedentary (SED) conditions for a total of four groups...
May 22, 2018: Medicine and Science in Sports and Exercise
Yung-Ting Kuo, Jhong-Huei Jheng, Mei-Chen Lo, Wei-Lu Chen, Shyang-Guang Wang, Horng-Mo Lee
Iron or oxygen regulates the stability of hypoxia inducible factor-1α (HIF-1α). We investigated whether ferrous glycinate would affect HIF-1α accumulation, aerobic glycolysis and mitochondrial energy metabolism in human A549 lung cancer cells. Incubation of A549 cells with ferrous glycinate decreased the protein levels of HIF-1α, which was abrogated by proteosome inhibitor, or prolyl hydroxylase inhibitor. Addition of ferrous glycinate decreased protein levels of glucose transporter-1, hexokinase-2, and lactate dehydrogenase A, and decreased pyruvate dehydrogenase kinase-1 (PDK-1) and pyruvate dehydrogenase (PDH) phosphorylation in A549 cells...
May 15, 2018: Free Radical Research
Daiane G Franco, Isabele F Moretti, Suely K N Marie
The disruption of mitochondrial activity has been associated with cancer development because it contributes to regulating apoptosis and is the main source of reactive oxygen species (ROS) production. Mitochondrial transcription factor A (TFAM) is a protein that maintains mitochondrial DNA (mtDNA) integrity, and alterations in its expression are associated with mitochondrial damage and cancer development. In addition, studies have shown that mitochondria are a known target of melatonin, the pineal gland hormone that plays an important anti-tumorigenic role...
May 9, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Kirsty Foote, Johannes Reinhold, Emma P K Yu, Nichola L Figg, Alison Finigan, Michael P Murphy, Martin R Bennett
Aging is the largest risk factor for cardiovascular disease, yet the molecular mechanisms underlying vascular aging remain unclear. Mitochondrial DNA (mtDNA) damage is linked to aging, but whether mtDNA damage or mitochondrial dysfunction is present and directly promotes vascular aging is unknown. Furthermore, mechanistic studies in mice are severely hampered by long study times and lack of sensitive, repeatable and reproducible parameters of arterial aging at standardized early time points. We examined the time course of multiple invasive and noninvasive arterial physiological parameters and structural changes of arterial aging in mice, how aging affects vessel mitochondrial function, and the effects of gain or loss of mitochondrial function on vascular aging...
May 9, 2018: Aging Cell
Jian Yin, Jiabin Guo, Qiang Zhang, Lan Cui, Li Zhang, Tingfen Zhang, Jun Zhao, Jin Li, Alistair Middleton, Paul L Carmichael, Shuangqing Peng
The usefulness of doxorubicin (DOX), a potent anticancer agent, is limited by its cardiotoxicity. Mitochondria play a central role in DOX-induced cardiotoxicity though the precise mechanisms are still obscure. Increasing evidence indicates that excessive activation of mitophagy and mitochondrial dysfunction are key causal events leading to DOX-induced cardiac injury. The PINK1/parkin pathway has emerged as a critical pathway in regulation of mitophagy as well as mitochondrial function. The present study was aimed to investigate the role of PINK1/parkin pathway in DOX-induced mitochondrial damage and cardiotoxicity...
May 3, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Andrea Dlasková, Hana Engstová, Tomáš Špaček, Anežka Kahancová, Vojtěch Pavluch, Katarína Smolková, Jitka Špačková, Martin Bartoš, Lydie Plecitá Hlavatá, Petr Ježek
3D super-resolution microscopy based on the direct stochastic optical reconstruction microscopy (dSTORM) with primary Alexa-Fluor-647-conjugated antibodies is a powerful method for accessing changes of objects that could be normally resolved only by electron microscopy. Despite the fact that mitochondrial cristae yet to become resolved, we have indicated changes in cristae width and/or morphology by dSTORM of ATP-synthase F1 subunit α (F1 α). Obtained 3D images were analyzed with the help of Ripley's K-function modeling spatial patterns or transferring them into distance distribution function...
May 1, 2018: Biochimica et Biophysica Acta
M Fiorenza, T P Gunnarsson, M Hostrup, F M Iaia, F Schena, H Pilegaard, J Bangsbo
KEY POINTS: Low-volume high-intensity exercise training promotes muscle mitochondrial adaptations that resemble the ones associated with high-volume moderate-intensity exercise training. These training-induced mitochondrial adaptations stem from the cumulative effects of transient transcriptional responses to each acute exercise bout. However, whether metabolic stress is a key mediator of the acute molecular responses to high-intensity exercise is still incompletely understood. Herein we show that, by comparing different work-matched low-volume high-intensity exercise protocols, more marked metabolic perturbations were associated with enhanced mitochondrial biogenesis-related muscle mRNA responses...
May 4, 2018: Journal of Physiology
Li-Jun Zhao, Shi-Fang Zhang
Impairment of mitochondrial biogenesis has been associated with vascular pathophysiology. The G-protein-coupled receptor (TGR5) is an important mediator of bile acid signaling and glucose metabolism. However, the effects of TGR5 on mitochondrial biogenesis in endothelial cells remain elusive. In this study, we found that activation of TGR5 using its specific agonist taurolithocholic acid (TLCA) promoted the expression of PGC-1α, a master regulator of mitochondrial biogenesis in human aortic endothelial cells (HAECs)...
June 12, 2018: Biochemical and Biophysical Research Communications
P Hemachandra Reddy, XiangLin Yin, Maria Manczak, Subodh Kumar, Pradeepkiran Jangampalli Adi, Murali Vijayan, Arubala P Reddy
The purpose of our study was to determine the toxic effects of hippocampal mutant APP and amyloid beta (Aβ) in human mutant APP (mAPP) cDNA transfected with primary mouse hippocampal neurons (HT22). Hippocampal tissues are the best source of studying learning and memory functions in patients with Alzheimer's disease (AD) and healthy controls. However, investigating immortalized hippocampal neurons that express AD proteins provide an excellent opportunity for drug testing. Using quantitative RT-PCR, immunoblotting & immunofluorescence, and transmission electron microscopy, we assessed mRNA and protein levels of synaptic, autophagy, mitophagy, mitochondrial dynamics, biogenesis, dendritic protein MAP2, and assessed mitochondrial number and length in mAPP-HT22 cells that express Swedish/Indiana mutations...
April 25, 2018: Human Molecular Genetics
Kaori Ogawa, Nobuhiko Itami, Manami Ueda, Kazuki Kansaku, Koumei Shirasuna, Takehito Kuwayama, Hisataka Iwata
Purpose: The effect of supplementing maturation medium with follicular fluid (FF) was examined according to its non-esterified fatty acid (NEFA) content or with a fatty acid mixture (FA-Mix) on the developmental competence of oocytes, as well as the mitochondrial quality and quantity in the oocytes and cumulus cells. Method: Porcine oocytes from a slaughterhouse were used. Results: The FF or FA-Mix in maturation medium increased the lipid content in both the oocytes and the cumulus cells, but the adenosine triphosphate content was differentially affected...
April 2018: Reproductive Medicine and Biology
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