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https://www.readbyqxmd.com/read/28339017/sirt1-is-required-for-mitochondrial-biogenesis-reprogramming-in-hypoxic-human-pulmonary-arteriolar-smooth-muscle-cells
#1
Pengyun Li, Yan Liu, Nana Burns, Ke-Seng Zhao, Rui Song
Although recent studies have reported that mitochondria are putative oxygen sensors underlying hypoxic pulmonary vasoconstriction, little is known concerning the sirtuin 1 (SIRT1)-mediated mitochondrial biogenesis regulatory program in pulmonary arteriolar smooth muscle cells (PASMCs) during hypoxia/reoxygenation (H/R). We investigated the epigenetic regulatory mechanism of mitochondrial biogenesis and function in human PASMCs during H/R. Human PASMCs were exposed to hypoxia of 24-48 h and reoxygenation of 24-48 h...
March 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28338198/the-expression-of-sirt3-in-primary-hepatocellular-carcinoma-and-the-mechanism-of-its-tumor-suppressing-effects
#2
Y Liu, Y-L Liu, W Cheng, X-M Yin, B Jiang
OBJECTIVE: To observe the SIRT 3 expression in primary hepatocellular carcinoma (HCC), and then establish the eukaryotic expression vector of SIRT3 to observe the proliferation and apoptosis of pZsGreen-c1-SIRT3 HepG2 cells. Furthermore, we explored the mechanism of SIRT3 in inhibiting HCC. PATIENTS AND METHODS: Immunohistochemistry was used to detect the expression of SIRT3 in the tumor tissue and para-tumor tissue in 32 patients with HCC and the normal liver tissue in 10 patients...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28323907/resveratrol-inhibits-androgen-production-of-human-adrenocortical-h295r-cells-by-lowering-cyp17-and-cyp21-expression-and-activities
#3
Nesa Marti, Nadia Bouchoucha, Kay-Sara Sauter, Christa E Flück
Resveratrol, a natural compound found in grapes, became very popular for its suggested protective effects against aging. It was reported to have similar positive effects on the human metabolism as caloric restriction. Recently, positive effects of resveratrol on steroid biosynthesis in cell systems and in humans suffering from polycystic ovary syndrome have also been reported, but the exact mechanism of this action remains unknown. Sirtuins seem targeted by resveratrol to mediate its action on energy homeostasis...
2017: PloS One
https://www.readbyqxmd.com/read/28302481/metformin-improves-cardiac-function-in-mice-with-heart-failure-after-myocardial-infarction-by-regulating-mitochondrial-energy-metabolism
#4
Dan Sun, Fei Yang
To investigate whether metformin can improve the cardiac function through improving the mitochondrial function in model of heart failure after myocardial infarction. Male C57/BL6 mice aged about 8 weeks were selected and the anterior descending branch was ligatured to establish the heart failure model after myocardial infarction. The cardiac function was evaluated via ultrasound after 3 days to determine the modeling was successful, and the mice were randomly divided into two groups. Saline group (Saline) received the intragastric administration of normal saline for 4 weeks, and metformin group (Met) received the intragastric administration of metformin for 4 weeks...
March 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28301150/discovery-of-new-sirt2-inhibitors-by-utilizing-a-consensus-docking-scoring-strategy-and-structure-activity-relationship-analysis
#5
Shen-Zhen Huang, Chun-Li Song, Xiang Wang, Guo Zhang, Yan-Lin Wang, Xiao-Juan Jiang, Qi-Zheng Sun, Lu-Yi Huang, Rong Xiang, Yi-Guo Hu, Lin-Li Li, Sheng-Yong Yang
SIRT2, which is a NAD+ (nicotinamide adenine dinucleotide)-dependent deacetylase, has been demonstrated to play an important role in the occurrence and development of a variety of diseases such as cancer, ischemia-reperfusion, and neurodegenerative diseases. Small molecule inhibitors of SIRT2 are thought as potential interfering agents for relevant diseases. Discovery of SIRT2 inhibitor has attracted much attention recently. In this investigation, we first adopted a consensus docking/scoring strategy to screen for novel SIRT2 inhibitors...
March 16, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28296597/acetylation-targets-hsd17b4-for-degradation-via-the-cma-pathway-in-response-to-estrone
#6
Ye Zhang, Ying-Ying Xu, Chuan-Bo Yao, Jin-Tao Li, Xiang-Ning Zhao, Hong-Bin Yang, Min Zhang, Miao Yin, Jing Chen, Qun-Ying Lei
Dysregulation of hormone metabolism is implicated in human breast cancer. 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4) catalyzes the conversion of estradiol (E2) to estrone (E1), and is associated with the pathogenesis and development of various cancers. Here we show that E1 upregulates HSD17B4 acetylation at lysine 669 (K669) and thereby promotes HSD17B4 degradation via chaperone-mediated autophagy (CMA), while a single mutation at K669 reverses the degradation and confers migratory and invasive properties to MCF7 cells upon E1 treatment...
March 4, 2017: Autophagy
https://www.readbyqxmd.com/read/28296029/cd38-promotes-angiotensin-ii-induced-cardiac-hypertrophy
#7
Xiao-Hui Guan, Xuan Hong, Ning Zhao, Xiao-Hong Liu, Yun-Fei Xiao, Ting-Tao Chen, Li-Bin Deng, Xiao-Lei Wang, Jian-Bin Wang, Guang-Ju Ji, Mingui Fu, Ke-Yu Deng, Hong-Bo Xin
Cardiac hypertrophy is an early hallmark during the clinical course of heart failure and regulated by various signalling pathways. Recently, we observed that mouse embryonic fibroblasts from CD38 knockout mice were significantly resistant to oxidative stress such as H2 O2 -induced injury and hypoxia/reoxygenation-induced injury. In addition, we also found that CD38 knockout mice protected heart from ischaemia reperfusion injury through activating SIRT1/FOXOs-mediated antioxidative stress pathway. However, the role of CD38 in cardiac hypertrophy is not explored...
March 12, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28286268/resveratrol-rescues-cadmium-induced-mitochondrial-injury-by-enhancing-transcriptional-regulation-of-pgc-1%C3%AE-and-sod2-via-the-sirt3-foxo3a-pathway-in-tcmk-1-cells
#8
Beibei Fu, Jiamin Zhao, Wei Peng, Haibo Wu, Yong Zhang
Resveratrol has been reported to ameliorate Cd-induced nephrotoxicity. However, the beneficial effects of resveratrol on Cd-induced nephrotoxicity and the underlying mechanisms of this protection remain unclear. Here, we showed that mouse renal tubular epithelial (TCMK-1) cells exposed to Cd experienced significantly increased mitochondrial reactive oxygen species (mROS) production, as well as decreased mitochondrial biogenesis and function. Cd exposure dramatically decreased Sirt3 protein expression and activity and promoted the acetylation of forkhead box O3 (FoxO3a)...
April 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28285806/mitochondrial-sirtuins-and-molecular-mechanisms-of-aging
#9
REVIEW
Robert A H van de Ven, Daniel Santos, Marcia C Haigis
Advancing age is the major risk factor for the development of chronic diseases and is accompanied by changes in metabolic processes and mitochondrial dysfunction. Mitochondrial sirtuins (SIRT3-5) are part of the sirtuin family of NAD(+)-dependent deacylases and ADP-ribosyl transferases. The dependence on NAD(+) links sirtuin enzymatic activity to the metabolic state of the cell, poising them as stress sensors. Recent insights have revealed that SIRT3-5 orchestrate stress responses through coordinated regulation of substrate clusters rather than of a few key metabolic enzymes...
March 9, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28276426/microrna-92a-is-a-circadian-modulator-of-neuronal-excitability-in-drosophila
#10
Xiao Chen, Michael Rosbash
Many biological and behavioural processes of animals are governed by an endogenous circadian clock, which is dependent on transcriptional regulation. Here we address post-transcriptional regulation and the role of miRNAs in Drosophila circadian rhythms. At least six miRNAs show cycling expression levels within the pigment dispersing factor (PDF) cell-pacemaker neurons; only mir-92a peaks during the night. In vivo calcium monitoring, dynamics of PDF projections, ArcLight, GCaMP6 imaging and sleep assays indicate that mir-92a suppresses neuronal excitability...
March 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28274921/the-unfolded-protein-response-in-relation-to-mitochondrial-biogenesis-in-skeletal-muscle-cells
#11
Zahra S Mesbah Moosavi, David A Hood
Mitochondria are comprised of both nuclear- and mitochondrially-encoded proteins requiring precise stoichiometry for their integration into functional complexes. The augmented protein synthesis associated with mitochondrial biogenesis results in the accumulation of unfolded proteins, thus triggering cellular stress. As such, the unfolded protein responses emanating from the endoplasmic reticulum (UPR(ER)) or the mitochondrion (UPR(MT)) are triggered to ensure correct protein handling. Whether this response is necessary for mitochondrial adaptations is unknown...
March 8, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28258190/sirt3-deficiency-promotes-lung-fibrosis-by-augmenting-alveolar-epithelial-cell-mitochondrial-dna-damage-and-apoptosis
#12
Renea P Jablonski, Seok-Jo Kim, Paul Cheresh, David B Williams, Luisa Morales-Nebreda, Yuan Cheng, Anjana Yeldandi, Sangeeta Bhorade, Annie Pardo, Moises Selman, Karen Ridge, David Gius, G R Scott Budinger, David W Kamp
Alveolar epithelial cell (AEC) mitochondrial dysfunction and apoptosis are important in idiopathic pulmonary fibrosis and asbestosis. Sirtuin 3 (SIRT3) detoxifies mitochondrial reactive oxygen species, in part, by deacetylating manganese superoxide dismutase (MnSOD) and mitochondrial 8-oxoguanine DNA glycosylase. We reasoned that SIRT3 deficiency occurs in fibrotic lungs and thereby augments AEC mtDNA damage and apoptosis. Human lungs were assessed by using immunohistochemistry for SIRT3 activity via acetylated MnSOD(K68) Murine AEC SIRT3 and cleaved caspase-9 (CC-9) expression were assayed by immunoblotting with or without SIRT3 enforced expression or silencing...
March 3, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28255277/sirtuin-3-is-required-for-osteogenic-differentiation-through-maintenance-of-pgc-1%C3%A9-sod2-mediated-regulation-of-mitochondrial-function
#13
Yong Ding, Hongmei Yang, Yucai Wang, Jun Chen, Zhenwei Ji, Honghui Sun
Osteogenic differentiation is crucial for the maintenance of bone homeostasis. Sirtuin 3 (SIRT3), a member of sirtuins family, functions as a critical deacetylase that regulates many key proteins. In the current study, we aimed to clarify the role of SIRT3 in osteogenic differentiation and the possible mechanisms, using mouse pre-osteoblastic MC3T3-E1 cells. Expression of SIRT3 was substantially increased in differentiated MC3T3-E1 cells. Knock down of SIRT3 significantly decreased alkaline phosphatase (ALP) staining, and mRNA expression of runt-related transcription factor 2 (Runx2) and collagen type I ɑ 1 (Col1ɑ1), and osteocalcin in differentiated MC3T3-E1 cells...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28254776/accurate-quantification-of-site-specific-acetylation-stoichiometry-reveals-the-impact-of-sirtuin-deacetylase-cobb-on-the-e-coli-acetylome
#14
Brian Tate Weinert, Shankha Satpathy, Bogi Karbech Hansen, David Lyon, Lars Juhl Jensen, Chunaram Choudhary
Lysine acetylation is a protein posttranslational modification (PTM) that occurs on thousands of lysine residues in diverse organisms from bacteria to humans. Accurate measurement of acetylation stoichiometry on a proteome-wide scale remains challenging. Most methods employ a comparison of chemically acetylated peptides to native acetylated peptides, however, the potentially large differences in abundance between these peptides presents a challenge for accurate quantification. Stable isotope labeling by amino acids in cell culture (SILAC)-based mass spectrometry (MS) is one of the most widely used quantitative proteomic methods...
March 2, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28253987/metabolic-syndrome-and-the-cellular-phase-of-alzheimer-s-disease
#15
S Pugazhenthi
Alzheimer's disease (AD) is characterized by cognitive dysfunction and progressive neurodegeneration. The major hallmarks of AD pathology are amyloid plaques and neurofibrillary tangles. However, AD often coexists with other brain microvascular lesions caused by comorbidities, including obesity, diabetes, hypertension, and cardiovascular diseases. The risk factors for these comorbidities are collectively referred to as metabolic syndrome (MetS). Clinical AD is preceded by decades of prodromal cellular phase...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28253192/the-role-of-sirtuins-in-mitochondrial-function-and-doxorubicin-induced-cardiac-dysfunction
#16
Vernon W Dolinsky
Anthracycline chemotherapeutics such as doxorubicin continue to be important treatments for many cancers. Through improved screening and therapy more patients are surviving and living longer after the diagnosis of their cancer. However, anthracyclines are associated with both short- and long-term cardiotoxic effects. Doxorubicin-induced mitochondrial dysfunction is a central mechanism in the cardiotoxic effects of doxorubicin that contributes to impaired cardiac energy levels, increased reactive oxygen species production, cardiomyocyte apoptosis and the decline in cardiac function...
March 2, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28249157/non-enzymatic-n-acetylation-of-lysine-residues-by-acetylcoa-often-occurs-via-a-proximal-s-acetylated-thiol-intermediate-sensitive-to-glyoxalase-ii
#17
Andrew M James, Kurt Hoogewijs, Angela Logan, Andrew R Hall, Shujing Ding, Ian M Fearnley, Michael P Murphy
Acetyl coenzyme A (AcCoA), a key intermediate in mitochondrial metabolism, N-acetylates lysine residues, disrupting and, in some cases, regulating protein function. The mitochondrial lysine deacetylase Sirtuin 3 (Sirt3) reverses this modification with benefits reported in diabetes, obesity, and aging. We show that non-enzymatic lysine N-acetylation by AcCoA is greatly enhanced by initial acetylation of a cysteine residue, followed by SN-transfer of the acetyl moiety to a nearby lysine on mitochondrial proteins and synthetic peptides...
February 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28248093/characterizing-sirtuin-3-deacetylase-affinity-for-aldehyde-dehydrogenase-2
#18
Peter S Harris, Joe D Gomez, Donald S Backos, Kristofer S Fritz
Mitochondrial aldehyde dehydrogenase (ALDH2) plays a central role in the detoxification of reactive aldehydes generated through endogenous and exogenous sources. The biochemical regulation of enzyme activity through post-translational modification provides an intricate response system regulating mitochondrial detoxification pathways. ALDH2 is a known target of lysine acetylation, which arises as a consequence of mitochondrial bioenergetic flux and sirtuin deacetylase activity. The mitochondrial deacetylase Sirtuin 3 (SIRT3) has been reported to alter ALDH2 lysine acetylation status, yet the mechanism and consequence of this interaction remain unknown...
March 1, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28239025/the-role-of-single-nucleotide-variants-of-the-energy-metabolism-linked-genes-sirt3-ppargc1a-and-apoe-in-amyotrophic-lateral-sclerosis-risk
#19
Diego Albani, Elisabetta Pupillo, Elisa Bianchi, Armando Chierchia, Rosalba Martines, Gianluigi Forloni, Ettore Beghi
Amyotrophic lateral sclerosis (ALS) is a multifactorial disease, possibly with contributions from genetics and lifestyle. We examined variants in genes relevant to energy metabolism and physical activity in a case-control association study, with the aim of assessing genetics and physical activity as contributors to ALS risk. A well-characterized sample of Italian ALS patients (101) and controls (101) from the EURALS Consortium underwent a questionnaire interview on demographic, physical and other lifestyle habits, and venipuncture for DNA extraction...
February 24, 2017: Genes & Genetic Systems
https://www.readbyqxmd.com/read/28236057/regulation-of-sirtuin-3-mediated-deacetylation-of-cyclophilin-d-attenuated-cognitive-dysfunction-induced-by-sepsis-associated-encephalopathy-in-mice
#20
Fan Sun, Yanna Si, Hongguang Bao, Yajie Xu, XiaoXiao Pan, Lingqing Zeng, Ling Jing
The present study aimed to investigate cognitive dysfunction in the hippocampus induced by sepsis-associated encephalopathy (SAE) via acetylation of cyclophilin D (CypD) and opening of mitochondrial permeability transition pore. It also explored whether activating sirtuin 3 (SIRT3) can mediate deacetylation of CypD and prevent the development of SAE. Male mice were randomly assigned to six groups: sham group, cecal ligation puncture group, CypD siRNA transfection (CypD-si) group, CypD control siRNA transfection (CypD-c) group, SIRT3 overexpression vector pcDNA3...
February 25, 2017: Cellular and Molecular Neurobiology
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