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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
R Bescos, M J Boden, M L Jackson, A J Trewin, E C Marin, I Levinger, A Garnham, D S Hiam, F Falcao-Tebas, F Conte, J A Owens, D J Kennaway, G K McConell
AIM: The aim of this study was to investigate the effects of four consecutive simulated night shifts on glucose homeostasis, mitochondrial function and central and peripheral rhythmicity compared with a simulated day shift schedule. METHODS: Seventeen healthy adults (8M:9F) matched for sleep, physical activity, and dietary/fat intake participated in this study (night shift work n= 9; day shift work n= 8). Glucose tolerance and insulin sensitivity before and after 4 nights of shift work were measured by an intravenous glucose tolerance test and a hyperinsulinemic euglycemic clamp, respectively...
January 22, 2018: Acta Physiologica
Aldo Moreno-Ulloa, Adriana Miranda-Cervantes, Alexei Licea-Navarro, Christina Mansour, Ernesto Beltrán-Partida, Luis Donis-Maturano, Hilda Carolina Delgado De la Herrán, Francisco Villarreal, Carolina Álvarez-Delgado
We have reported on the capacity of (-)-epicatechin ((-)-EPI) to stimulate mitochondrial biogenesis (MiB) in mouse skeletal muscle (SkM). However, the mechanisms mediating the effects of (-)-EPI are not fully understood. We previously identified a role of the G-protein coupled estrogen receptor (GPER) in modulating the vascular effects of (-)-EPI. We therefore tested the hypothesis that GPER mediates (at least in part) the stimulatory effects of (-)-EPI on MiB in SkM cells. As an in vitro model, we employed mouse SkM-derived C2C12 myoblasts differentiated into myotubes...
January 16, 2018: European Journal of Pharmacology
Inderjit Singh, Devadoss J Samuvel, Seungho Choi, Nishant Saxena, Avtar K Singh, Jeseong Won
Recent studies report that loss and dysfunction of mitochondria and peroxisomes contribute to the myelin and axonal damage in multiple sclerosis (MS). In this study, we investigated the efficacy of lovastatin and AMPK activator (AICAR) combination on the loss and dysfunction of mitochondria and peroxisomes and myelin and axonal damage in the spinal cords, relative to the clinical disease symptoms, using a mouse model of experimental autoimmune encephalomyelitis (EAE, a model for MS). We observed that lovastatin and AICAR treatments individually provided partial protection of mitochondria/peroxisomes, myelin/axons, and thus partial attenuation of clinical disease in EAE mice...
January 13, 2018: Immunology
Nanhu Quan, Lin Wang, Xu Chen, Chelsea Luckett, Courtney Cates, Thomas Rousselle, Yang Zheng, Ji Li
We have revealed that a novel stress-inducible protein, Sestrin2, declines in the heart with aging. Moreover, there is an interaction between Sestrin2 and energy sensor AMPK in the heart in response to ischemic stress. The objective of this study is to determine whether Sestrin2-AMPK complex modulates PGC-1α in the heart and protects the heart from ischemic insults. In order to characterize the role of cardiac Sestrin2-AMPK signaling cascade in aging, C57BL/6 wild type young mice (3-4months), aged mice (24-26months) and young Sestrin2 KO mice were subjected to left anterior descending coronary artery occlusion for in vivo regional ischemia...
January 8, 2018: Journal of Molecular and Cellular Cardiology
Kaitlyn Beyfuss, David A Hood
BACKGROUND: p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis. METHODS: A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases...
January 3, 2018: Redox Report: Communications in Free Radical Research
Krish Chandrasekaran, Anjaneyulu Muragundla, Tyler G Demarest, Joungil Choi, Avinash R Sagi, Neda Najimi, Pranith Kumar, Anmol Singh, Cheng-Ying Ho, Gary Fiskum, Lauren G Koch, Steven L Britton, James W Russell
Objectives: There is a critical need to develop effective treatments for diabetic neuropathy. This study determined if a selective mGluR2/3 receptor agonist prevented or treated experimental diabetic peripheral neuropathy (DPN) through glutamate recycling and improved mitochondrial function. Methods: Adult male streptozotocin treated Sprague-Dawley rats with features of type 1 diabetes mellitus (T1DM) or Low Capacity Running (LCR) rats with insulin resistance or glucose intolerance were treated with 3 or 10 mg/kg/day LY379268...
December 2017: Annals of Clinical and Translational Neurology
Lingling Zhou, Cong Zhou, Zhe Feng, Zhangpu Liu, Huaxu Zhu, Xueping Zhou
ETHNOPHARMACOLOGICAL RELEVANCE: The hepatotoxicity of Tripterygium wilfordii Hook. f. (TW), due to the presence of triptolide (TP), limits its therapeutic potential. Based on the traditional Chinese medicine theory, the theory of "Yi lei xiang zhi" was proposed that Chinese herbs with different efficacy can restrict each other to achieve the least adverse reactions. AIM OF THE STUDY: To observe the effects of Catapol (CAT) and Panax notoginseng saponins (PNS), active ingredients in Rehmannia glutinosa (RG) and Panax notoginseng (PN) respectively, on reducing TP-induced hepatotoxicity, and further to explore the mechanisms...
December 22, 2017: Journal of Ethnopharmacology
Woo Rin Lee, Heeju Na, Seon Woo Lee, Won-Jun Lim, Namshin Kim, J Eugene Lee, Changwon Kang
Human mitochondrial transcription factor A (TFAM) has been implicated in promoting tumor growth and invasion. TFAM activates mitochondrial DNA (mtDNA) transcription, and affects nuclear gene expression through mitochondrial retrograde signaling. In this study, we investigated the effects of TFAM depletion on the morphology and transcriptome of MKN45 gastric cancer cells. Morphology alteration became visible at 12 h after TFAM knockdown: the proportion of growth-arrested polygonal cells versus oval-shaped cells increased, reaching a half-maximum at 24 h and a near-maximum at 36 h...
December 19, 2017: Scientific Reports
Anna Rubio-Cosials, Federica Battistini, Alexander Gansen, Anna Cuppari, Pau Bernadó, Modesto Orozco, Jörg Langowski, Katalin Tóth, Maria Solà
Human mitochondrial transcription factor A (TFAM) distorts DNA into a U-turn, as shown by crystallographic studies. The relevance of this U-turn is associated with transcription initiation at the mitochondrial light strand promoter (LSP). However, it has not been yet discerned whether a tight U-turn or an alternative conformation, such as a V-shape, is formed in solution. Here, single-molecule FRET experiments on freely diffusing TFAM/LSP complexes containing different DNA lengths show that a DNA U-turn is induced by progressive and cooperative binding of the two TFAM HMG-box domains and the linker between them...
December 13, 2017: Biophysical Journal
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