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Yulai Shen, Lu Wu, Dongdong Qin, Yankai Xia, Zhu Zhou, Xuemei Zhang, Xin Wu
BACKGROUND: The rapid increase in carbon black poses threats to human health. We evaluated the effect of CB (Printex 90) on the osteogenesis of bone-marrow-derived mesenchymal stem cells (MSCs). Mitochondria play an important role in the osteogenesis of MSCs and are potential targets of nanomaterials, so we studied the role of mitochondria in the CB Printex 90-induced effects on osteogenesis. RESULTS: Low doses of Printex 90 (3 ng/mL and 30 ng/mL) that did not cause deleterious effects on MSCs' viability significantly inhibited osteogenesis of MSCs...
April 12, 2018: Particle and Fibre Toxicology
Meghan G Patton, Trevor L Gillum, Mandy C Szymanski, Lacey M Gould, Claire J Lauterbach, Roger A Vaughan, Matthew R Kuennen
This work investigated the effect of a 6-day heat acclimation (HA) protocol on myotube metabolic responses at baseline and in response to a subsequent lipopolysaccharide (LPS) challenge. C2C12 myotubes were incubated for 2 h/day at 40 °C for 6 days (HA) or maintained at 37 °C (C). Following 24-h recovery, myotubes were challenged with 500 ng/ml LPS for 2 h, then collected for analysis of protein markers of mitochondrial biogenesis and macronutrient storage. Functional significance of these changes was confirmed with mitochondrial respiration and glycolytic measurements on a Seahorse XF-96 analyzer...
April 11, 2018: Cell Stress & Chaperones
Diana Vargas, Carolina López, Edward Acero, Edgar Benitez, Angélica Wintaco, Jaime Camacho, Marisol Carreño, Juan Umaña, Daniela Jimenez, Said Díaz, Fernando Lizcano
The anatomical location of adipose tissue might have direct implications for its functionality and risk of cardiovascular disease. Adipose tissue surrounding blood vessels may be thermogenically more active in specific areas of the body, releasing substances that regulate vascular metabolism. In humans, the phenotypic characteristics of adipose tissue surrounding the aorta and the cardiovascular disease risk that it might entail remain largely unknown. Here, we compared thermogenesis-related molecular features of human periaortic adipose tissue samples with those of subcutaneous adipose tissue, obtained by sternotomy from 42 patients undergoing cardiovascular surgery...
2018: PloS One
Qiongyuan Hu, Jianan Ren, Guanwei Li, Jie Wu, Xiuwen Wu, Gefei Wang, Guosheng Gu, Huajian Ren, Zhiwu Hong, Jieshou Li
Disruption of the mucosal barrier following intestinal ischemia reperfusion (I/R) is life threatening in clinical practice. Mitochondrial dysfunction and oxidative stress significantly contribute to the early phase of I/R injury and amplify the inflammatory response. MitoQ is a mitochondrially targeted antioxidant that exerts protective effects following I/R injury. In the present study, we aimed to determine whether and how MitoQ protects intestinal epithelial cells (IECs) from I/R injury. In both in vivo and in vitro studies, we found that MitoQ pretreatment downregulated I/R-induced oxidative stress and stabilized the intestinal barrier, as evidenced by MitoQ-treated I/R mice exhibiting attenuated intestinal hyperpermeability, inflammatory response, epithelial apoptosis, and tight junction damage compared to controls...
March 14, 2018: Cell Death & Disease
Li Gan, Delin Ma, Min Li, Fu-Chen Yang, Robert S Rogers, Joshua L Wheatley, Lauren G Koch, Steven L Britton, John P Thyfault, Paige C Geiger, John A Stanford
Aerobic capacity is a strong predictor of mortality. Low capacity runner (LCR) rats exhibit reduced mitochondrial function in peripheral organs. A high fat diet (HFD) can worsen metabolic phenotype in LCR rats. Little is known about metabolic changes in the brains of these rats, however. This study examined protein markers of mitochondrial function and metabolism as a function of aerobic running capacity and an acute HFD in four brain regions: the striatum, hippocampus, hypothalamus, and substantia nigra. After 3 days HFD or chow diets, we measured peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1-α), nuclear respiratory factors 1 (Nrf-1), mitochondrial transcription factor A (TFAM), and phosphorylated (activated) AMP-activated protein kinase (p-AMPK) protein levels in the four brain regions...
March 6, 2018: Neuroscience Letters
Ruchi Masand, Esther Paulo, Dongmei Wu, Yangmeng Wang, Danielle L Swaney, David Jimenez-Morales, Nevan J Krogan, Biao Wang
Brown adipose tissue (BAT) thermogenesis is critical for thermoregulation and contributes to total energy expenditure. However, whether BAT has non-thermogenic functions is largely unknown. Here, we describe that BAT-specific liver kinase b1 knockout (Lkb1BKO ) mice exhibited impaired BAT mitochondrial respiration and thermogenesis but reduced adiposity and liver triglyceride accumulation under high-fat-diet feeding at room temperature. Importantly, these metabolic benefits were also present in Lkb1BKO mice at thermoneutrality, where BAT thermogenesis was not required...
March 6, 2018: Cell Metabolism
Yi-Xuan Guo, Hai-Tao Nie, Chen-Jie Xu, Guo-Min Zhang, Ling-Wei Sun, Ting-Ting Zhang, Zhen Wang, Xu Feng, Pei-Hua You, Feng Wang
The aim of this study was to determine whether nutrient restriction and arginine treatment affect energy metabolism changes and oxidative stress through the mitochondrial pathway in the ovarian tissue of ewes during the luteal phase. On days 6-15 of the estrous cycle, 24 multiparous Hu sheep (BW = 43.56 ± 1.53 kg) were randomly assigned to three groups: control group (CG; n = 6), restriction group (RG; n = 9), and l-arginine group (AG; n = 9) administered Arg treatment (or vehicle) three times per day...
February 22, 2018: Theriogenology
Martine Uittenbogaard, Christine A Brantner, Anne Chiaramello
During neural development, epigenetic modulation of chromatin acetylation is part of a dynamic, sequential and critical process to steer the fate of multipotent neural progenitors toward a specific lineage. Pan-HDAC inhibitors (HDCis) trigger neuronal differentiation by generating an "acetylation" signature and promoting the expression of neurogenic bHLH transcription factors. Our studies and others have revealed a link between neuronal differentiation and increase of mitochondrial mass. However, the neuronal regulation of mitochondrial biogenesis has remained largely unexplored...
March 2, 2018: Cell Death & Disease
Masanobu Tsuchiya, Toru Ichiseki, Shusuke Ueda, Yoshimichi Ueda, Miyako Shimazaki, Ayumi Kaneuji, Norio Kawahara
The purpose of the role of antioxidant enzymes and mitochondria in the developmental mechanism of steroid-associated osteonecrosis in the femur. In the present study Japanese white rabbits (mean weight 3.5kg) were injected into the gluteus with methylprednisolone (MP) 20mg/kg, and killed after 3 days (MP3 group), 5 days (MP5 group), and 14 days (MP14 group) (n=3 each). As a Control group (C group) Japanese white rabbits not administered MP were used. In experiment 1, the expression of the antioxidant enzymes Superoxide dismutade (SOD) and catalase was compared in liver, kidney, heart, humerus, and femur in C group, and the presence/absence of mitochondria transcription factor A (TFAM) expression was determined by Western blotting (WB) and used to evaluate the number of mitochondria and their function...
2018: International Journal of Medical Sciences
Wei Gao, Meihong Wu, Ning Wang, Yingyi Zhang, Jing Hua, Gusheng Tang, Yajie Wang
Nuclear respiratory factor-1 (Nrf1) and mitochondrial transcription factor A (TFAM) are involved in the regulation of a variety of mitochondrial functional genes, which are associated with decreased sensitivity of tumor cells to chemotherapy. However, the expression status of Nrf1 and TFAM, as well as their clinical significance in breast cancer, is unknown. In the present study, tumor tissues and corresponding adjacent normal tissues were collected from 336 patients with breast cancer, and Nrf1 and TFAM expression was analyzed by immunohistochemistry using a tissue microarray...
February 2018: Oncology Letters
Qingqing Qin, Jieqiong Jin, Fang He, Yongqin Zheng, Tingting Li, Yun Zhang, Jundong He
Mitochondrial dysfunction is associated with β-cell failure and insulin resistance in diabetes. Humanin is an endogenous cytoprotective peptide. In the current study, we aimed to define the effects of Humanin on mitochondrial biogenesis in pancreatic β-cells. Our findings demonstrated that Humanin treatment significantly increased the expression of PGC-1α and its downstream target genes NRF1 and TFAM in MIN6 β-cells. Notably, Humanin treatment significantly promoted mitochondrial biogenesis by increasing mitochondrial mass, elevating mtDNA/nDNA ratio, and stimulating the expression of cytochrome B, which were suppressed by the specific AMPK inhibitor compound C...
February 9, 2018: Biochemical and Biophysical Research Communications
Achim Sandmann, Heinrich Sticht
Protein binding can induce DNA kinks, which are for example important to enhance the specificity of the interaction and to facilitate the assembly of multi protein complexes. The respective proteins frequently exhibit amino acid sidechains that intercalate between the DNA base steps at the site of the kink. However, on a molecular level there is only little information available about the role of individual sidechains for kink formation. To unravel structural principles of protein-induced DNA kinking we have performed molecular dynamics (MD) simulations of five complexes that varied in their architecture, function, and identity of intercalated residues...
2018: PloS One
Maria Manczak, Ramesh Kandimalla, Xiangling Yin, P Hemachandra Reddy
The purpose of our study was to determine the toxic effects of hippocampal mutant APP and amyloid beta (Aβ) in 12-month-old APP transgenic mice. Using rotarod and Morris Water Maze tests, immunoblotting & immunofluorescence, Golgi-cox staining and transmission electron microscopy, we assessed cognitive behavior, protein levels of synaptic, autophagy, mitophagy, mitochondrial dynamics, biogenesis, dendritic protein MAP2, and quantified dendritic spines and mitochondrial number and length in 12-month-old APP mice that express swedish mutation...
February 1, 2018: Human Molecular Genetics
Rui Qi, Dongtao Wang, Lifei Xing, Zhongjun Wu
Dysregulation of mitochondrial biogenesis is associated with pathogenesis in many diseases, including liver diseases. Cyclosporine A (CsA), one of the most commonly used drug to treat many autoimmune diseases and to prevent allograft rejection after organ transplantation, has been reported to cause mitochondrial dysfunction. However, the cellular mechanisms underlying CsA on mitochondrial dysfunction remain at present not completely elucidated. In this study, we found that CsA reduced the expression of PGC-1α at both the mRNA and protein levels in HepG2 cells...
January 29, 2018: Biochemical and Biophysical Research Communications
Dennis K Fix, Justin P Hardee, Song Gao, Brandon N VanderVeen, Kandy T Velazquez, James A Carson
The IL-6 cytokine family activates intracellular signaling pathways through glycoprotein 130 (gp130), and this signaling has established regulatory roles in muscle glucose metabolism and proteostasis. Although the IL-6 family has been implicated as myokines regulating the muscle's metabolic response to exercise, gp130's role in mitochondrial quality control involving fission, fusion, mitophagy and biogenesis is not well understood. Therefore, we examined gp130's role in basal and exercise-trained muscle mitochondrial quality control...
February 1, 2018: Journal of Applied Physiology
Weiliang He, Yingping Liu, Xiaochao Tian
Neurogenesis, especially neurite outgrowth is an essential element of neuroplasticity after cerebral ischemic injury. Mitochondria may supply ATP to power fundamental developmental processes including neuroplasticity. Although rosuvastatin (RSV) displays a potential protective effect against cerebral ischemia, it remains unknown whether it modulates mitochondrial biogenesis and function during neurite outgrowth. Here, the oxygen-glucose deprivation (OGD) model was used to induce ischemic injury. We demonstrate that RSV treatment significantly increases neurite outgrowth in cortical neurons after OGD-induced damage...
2018: Frontiers in Cellular Neuroscience
Xiangrong Chen, Shun Li, Yumin Ke, Shukai Wu, Tianzao Huang, Weipeng Hu, Huangde Fu, Xieli Guo
BACKGROUND: This study aims to via unveiling the novel mechanisms of KLF16 in regulating expression of genes involved in glioma. METHODS: KLF16 or KLF16-siRNA was transfected to U87MG cells by lentivirus. Colony formation assay was applied for detecting cell proliferation. MTT assay was adopted to assess cell viability. TUNEL assay was selected to evaluate cell apoptosis. Flow cytometry was used to determine cell cycle. Real-time PCR was performed to test mRNA expression...
January 29, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Yogesh Rai, Richa Pathak, Neeraj Kumari, Dhananjay Kumar Sah, Sanjay Pandey, Namita Kalra, Ravi Soni, B S Dwarakanath, Anant Narayan Bhatt
Metabolic viability based high throughput assays like MTT and MTS are widely used in assessing the cell viability. However, alteration in both mitochondrial content and metabolism can influence the metabolic viability of cells and radiation is a potential mitochondrial biogenesis inducer. Therefore, we tested if MTT assay is a true measure of radiation induced cell death in widely used cell lines. Radiation induced cellular growth inhibition was performed by enumerating cell numbers and metabolic viability using MTT assay at 24 and 48 hours (hrs) after exposure...
January 24, 2018: Scientific Reports
Wenjing Wu, Jin Zhang, Chen Zhao, Yunmei Sun, Yajun Yin, Yongjia Peng, Weijun Pang, Gongshe Yang
The C1q/TNF-related protein 6 (CTRP6) is an adipokine involved in diverse biolgical processes. Formerly, we identified that CTRP6 regulates adipocyte differentiation, fatty acid oxidation and triglyceride accumulation in vitro. However, the effects of CTRP6 on adiposity in vivo have not yet been defined. This study aimed to confirm the involvement of CTRP6 in adipose accumulation and brown adipogenesis by intraperitoneal injection of the CTRP6-shRNA lentivirus into mice (CL mice). CL mice were significantly thinner than the control mice after feeding with a high fat diet (HFD), independent of food intake quantity...
January 20, 2018: Experimental Cell Research
Inhae Kang, Charleen T Chu, Brett A Kaufman
The mitochondrial transcription factor A, or TFAM, is a mitochondrial DNA (mtDNA) binding protein essential for genome maintenance. TFAM functions in determining the abundance of the mitochondrial genome by regulating packaging, stability, and replication. More recently, TFAM has been shown to play a central role in the mtDNA stress-mediated inflammatory response. Emerging evidence indicates that decreased mtDNA copy number is associated with several aging-related pathologies; however, little is known about the association of TFAM abundance and disease...
January 24, 2018: FEBS Letters
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