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https://www.readbyqxmd.com/read/28433661/differential-protein-acetylation-assists-import-of-excess-sod2-into-mitochondria-and-mediates-sod2-aggregation-associated-with-cardiac-hypertrophy-in-the-murine-sod2-tg-heart
#1
Liwen Zhang, Chwen-Lih Chen, Patrick T Kang, Zhicheng Jin, Yeong-Renn Chen
SOD2 is the primary antioxidant enzyme neutralizing ((•))O2((-)) in mitochondria. Cardiac-specific SOD2 overexpression (SOD2-tg) induces supernormal function and cardiac hypertrophy in the mouse heart. However, the reductive stress imposed by SOD2 overexpression results in protein aggregation of SOD2 pentamers and differential hyperacetylation of SOD2 in the mitochondria and cytosol. Here, we studied SOD2 acetylation in SOD2-tg and wild-type mouse hearts. LC-MS/MS analysis indicated the presence of four acetylated lysines in matrix SOD2 and nine acetylated lysines in cytosolic SOD2 from the SOD2-tg heart...
April 19, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28424621/activation-of-sirtuin-3-by-silybin-attenuates-mitochondrial-dysfunction-in-cisplatin-induced-acute-kidney-injury
#2
Yin Li, Zengchun Ye, Weiyan Lai, Jialing Rao, Wanbing Huang, Xiaohao Zhang, Ziying Yao, Tanqi Lou
Silybin is a secondary metabolite isolated from the seeds of blessed milk thistle (Silybum marianum) that has anti-inflammatory, antioxidative, antifibrotic, and antitumor properties. Here, we showed that silybin protected against cisplatin-induced acute kidney injury (AKI) by improving mitochondrial function through the regulation of sirtuin 3 (SIRT3) expression. Male SV129 and SIRT3 knockout (KO) mice were administered a single intraperitoneal (i.p.) injection of cisplatin with or without treatment with silybin...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28423723/honokiol-an-activator-of-sirtuin-3-sirt3-preserves-mitochondria-and-protects-the-heart-from-doxorubicin-induced-cardiomyopathy-in-mice
#3
Vinodkumar B Pillai, Abhinav Kanwal, Yong Hu Fang, Willard W Sharp, Sadhana Samant, Jack Arbiser, Mahesh P Gupta
Doxorubicin is the chemotherapeutic drug of choice for a wide variety of cancers, and cardiotoxicity is one of the major side effects of doxorubicin treatment. One of the main cellular targets of doxorubicin in the heart is mitochondria. Mitochondrial sirtuin, SIRT3 has been shown to protect against doxorubicin-induced cardiotoxicity. We have recently identified honokiol (HKL) as an activator of SIRT3, which protects the heart from developing pressure overload hypertrophy. Here, we show that HKL-mediated activation of SIRT3 also protects the heart from doxorubicin-induced cardiac damage without compromising the tumor killing potential of doxorubicin...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415012/discovery-of-2-4-6-dimethylpyrimidin-2-yl-thio-n-phenylacetamide-derivatives-as-new-potent-and-selective-human-sirtuin-2-inhibitors
#4
Lingling Yang, Xiaobo Ma, Chen Yuan, Yanying He, Ling Li, Sha Fang, Wei Xia, Tao He, Shan Qian, Zhihong Xu, Guobo Li, Zhouyu Wang
Human sirtuin 2 (SIRT2) plays pivotal roles in multiple biological processes such as cell cycle regulation, autophagy, immune and inflammatory responses. Dysregulation of SIRT2 was considered as a main aspect contributing to several human diseases, including cancer. Development of new potent and selective SIRT2 inhibitors is currently desirable, which may provide a new strategy for treatment of related diseases. Herein, a structure-based optimization approach led to new 2-((4,6-dimethylpyrimidin-2-yl)thio)-N-phenylacetamide derivatives as SIRT2 inhibitors...
April 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28411231/angiotensin-1-7-attenuates-angiotensin-ii-induced-cardiac-hypertrophy-via-a-sirt3-dependent-mechanism
#5
Lirong Guo, Ankang Yin, Qi Zhang, Tiecheng Zhong, Stephen T O'Rourke, Chengwen Sun
The objectives of the current study were to investigate the effect of Ang-(1-7) on the development of cardiac hypertrophy, and to identify the intracellular mechanism underlying this action of Ang-(1-7). Blood pressure and heart rate were recorded using radiotelemetry before and after chronic subcutaneous infusion of control (PBS), Ang II, Ang-(1-7), or Ang II+Ang-(1-7) for 4 weeks in normotensive rats. Chronic administration of Ang-(1-7) did not affect either basal blood pressure or the Ang II-induced elevation in blood pressure...
April 14, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28411102/zl006-protects-spinal-cord-neurons-against-ischemia-induced-oxidative-stress-through-ampk-pgc-1%C3%AE-sirt3-pathway
#6
Shu-Guang Liu, Yun-Mei Wang, Yan-Jun Zhang, Xi-Jing He, Tao Ma, Wei Song, Yu-Min Zhang
Spinal cord ischemia (SCI) induces a range of cellular and molecular cascades, including activation of glutamate receptors and downstream signaling. Post-synaptic density protein 95 (PSD-95) links neuronal nitric oxide synthase (nNOS) with the N-methyl-d-aspartic acid (NMDA) receptors to form a ternary complex in the CNS. This molecular complex-mediated cytotoxicity has been implicated in brain ischemia, but its role in SCI has not been determined. The goal of the study was to investigate the potential protective effects of ZL006, a small-molecule inhibitor of the PSD-95/nNOS interaction, in an in vitro SCI model induced by oxygen and glucose deprivation (OGD) in cultured spinal cord neurons...
April 12, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28400503/pgc-1%C3%AE-and-fasting-induced-pdh-regulation-in-mouse-skeletal-muscle
#7
Anders Gudiksen, Henriette Pilegaard
The purpose of the present study was to examine whether lack of skeletal muscle peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) affects the switch in substrate utilization from a fed to fasted state and the fasting-induced pyruvate dehydrogenase (PDH) regulation in skeletal muscle. Skeletal muscle-specific PGC-1α knockout (MKO) mice and floxed littermate controls were fed or fasted for 24 h. Fasting reduced PDHa activity, increased phosphorylation of all four known sites on PDH-E1α and increased pyruvate dehydrogenase kinase (PDK4) and sirtuin 3 (SIRT3) protein levels, but did not alter total acetylation of PDH-E1α Lack of muscle PGC-1α did not affect the switch from glucose to fat oxidation in the transition from the fed to fasted state, but was associated with lower and higher respiratory exchange ratio (RER) in the fed and fasted state, respectively...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28396567/inhibition-of-pikfyve-prevents-myocardial-apoptosis-and-hypertrophy-through-activation-of-sirt3-in-obese-mice
#8
Helene Tronchere, Mathieu Cinato, Andrei Timotin, Laurie Guitou, Camille Villedieu, Helene Thibault, Delphine Baetz, Bernard Payrastre, Philippe Valet, Angelo Parini, Oksana Kunduzova, Frederic Boal
PIKfyve is an evolutionarily conserved lipid kinase that regulates pleiotropic cellular functions. Here, we identify PIKfyve as a key regulator of cardiometabolic status and mitochondrial integrity in chronic diet-induced obesity. In vitro, we show that PIKfyve is critical for the control of mitochondrial fragmentation and hypertrophic and apoptotic responses to stress. We also provide evidence that inactivation of PIKfyve by the selective inhibitor STA suppresses excessive mitochondrial ROS production and apoptosis through a SIRT3-dependent pathway in cardiomyoblasts...
April 10, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28396174/sirt3-confers-protection-against-neuronal-ischemia-by-inducing-autophagy-involvement-of-the-ampk-mtor-pathway
#9
Shu-Hui Dai, Tao Chen, Xia Li, Kang-Yi Yue, Peng Luo, Li-Kun Yang, Jie Zhu, Yu-Hai Wang, Zhou Fei, Xiao-Fan Jiang
Sirtuin3 (Sirt3) is a member of the silent information regulator 2 (Sir2) family of proteins located in mitochondria that influences almost every major aspect of mitochondrial biology, including ATP generation and reactive oxygen species (ROS) production. Our previous study showed that Sirt3 exerts protective effects against oxidative stress in neuronal cells. In this study, we investigated the role of Sirt3 in neuronal ischemia using an oxygen and glucose deprivation (OGD) model. Sirt3 was up-regulated by OGD and overexpression of Sirt3 through lentivirus transfection significantly reduced OGD-induced lactate dehydrogenase (LDH) release and neuronal apoptosis...
April 7, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28387563/curcumin-upregulates-antioxidant-defense-lon-protease-and-heat-shock-protein-70-under-hyperglycemic-conditions-in-human-hepatoma-cells
#10
Shivona Gounden, Anil Chuturgoon
Sirtuin 3 (SIRT3) regulates mitochondrial antioxidant (AO) defense and improves mitochondrial disorders. Curcumin protects mitochondria; however, the mechanisms need investigation. We postulated that curcumin increases AO defense under hyperglycemic conditions in HepG2 cells through SIRT3-mediated mechanisms. Cell viability was determined in HepG2 cells cultured with 5 mM glucose, 19.9 mM mannitol, vehicle control, 10 mM glucose, and 30 mM glucose in the absence or presence of curcumin for 24 h. SIRT3, nuclear factor-kappa B (NF-κB), heat-shock protein 70 (Hsp70), and Lon protein expressions were determined using western blot...
April 7, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28386112/sodium-fluoride-induces-nephrotoxicity-via-oxidative-stress-regulated-mitochondrial-sirt3-signaling-pathway
#11
Chao Song, Beibei Fu, Jingcheng Zhang, Jiamin Zhao, Mengke Yuan, Wei Peng, Yong Zhang, Haibo Wu
Accumulation of mitochondrial reactive oxygen species (mROS) has been implicated in the pathogenesis of fluorosis. As the main mitochondrial deacetylase, SIRT3 is closely associated with oxidative stress. To investigate the role of SIRT3 in response to sodium fluoride (NaF)-induced nephrotoxicity. Our results showed that NaF treatment impaired mitochondrial ultrastructure, decreased cell viability and increased apoptosis in TCMK-1 cells. Oxidative stress, detected by mROS and 8-Hydroxy-2'-deoxyguanosine (8-OHdG) were higher in NaF-treated cells, accompanied by decreased level of reduced glutathione (GSH)...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28375738/sirt3-deficiency-increased-the-vulnerability-of-pancreatic-beta-cells-to-oxidative-stress-induced-dysfunction
#12
Yu Zhou, Arthur C K Chung, Rongrong Fan, Heung Man Lee, Gang Xu, Brian Tomlinson, Juliana C N Chan, Alice P S Kong
AIMS: Hyperlipidemia-induced oxidative stress is considered to be one of the main pathogenic factors that contribute to pancreatic beta cell dysfunction in the development of type 2 diabetes (T2D). Sirtuin 3 (Sirt3) is abundantly expressed in the mitochondria as an NAD(+)-dependent deacetylase and regulates mitochondrial adaptive responses to oxidative stress. We examined the antioxidant defense mechanism of Sirt3 in pancreatic beta cells in the context of hyperlipidemia. RESULTS: Chronic high-fat diet (HFD) feeding caused elevated oxidative stress accompanied by reduced Sirt3 expression in the pancreatic beta cells of wild-type mice...
April 4, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28369333/sirt3-protects-dopaminergic-neurons-from-mitochondrial-oxidative-stress
#13
Han Shi, Han-Xiang Deng, David Gius, Paul T Schumacker, D James Surmeier, Yong-Chao Ma
Age-dependent elevation in mitochondrial oxidative stress is widely posited to be a major factor underlying the loss of substantia nigra pars compacta (SNc) dopaminergic neurons in Parkinson's disease (PD). However, mechanistic links between aging and oxidative stress are not well understood. Sirtuin-3 (Sirt3) is a mitochondrial deacetylase that could mediate this connection. Indeed, genetic deletion of Sirt3 increased oxidative stress and decreased the membrane potential of mitochondria in SNc dopaminergic neurons...
March 24, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28368517/enhanced-glycolytic-metabolism-contributes-to-cardiac-dysfunction-in-polymicrobial-sepsis
#14
Zhibo Zheng, He Ma, Xia Zhang, Fei Tu, Xiaohui Wang, Tuanzhu Ha, Min Fan, Li Liu, Jingjing Xu, Kaiking Yu, Ruitao Wang, John Kalbfleisch, Race Kao, David Williams, Chuanfu Li
Background: Cardiac dysfunction is present in >40% of sepsis patients and is associated with mortality rates of up to 70%. Recent evidence suggests that glycolytic metabolism plays a critical role in host defense and inflammation. Activation of Toll-like receptors on immune cells can enhance glycolytic metabolism. This study investigated whether modulation of glycolysis by inhibition of hexokinase will be beneficial to septic cardiomyopathy. Methods: Male C57B6/J mice were treated with a hexokinase inhibitor (2-deoxy-D-glucose, 2-DG, 0...
March 22, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28368421/selected-mitochondrial-dna-landscapes-activate-the-sirt3-axis-of-the-upr-mt-to-promote-metastasis
#15
T C Kenny, P Hart, M Ragazzi, M Sersinghe, J Chipuk, M A K Sagar, K W Eliceiri, T LaFramboise, S Grandhi, J Santos, A K Riar, L Papa, M D'Aurello, G Manfredi, M G Bonini, D Germain
By causing mitochondrial DNA (mtDNA) mutations and oxidation of mitochondrial proteins, reactive oxygen species (ROS) leads to perturbations in mitochondrial proteostasis. Several studies have linked mtDNA mutations to metastasis of cancer cells but the nature of the mtDNA species involved remains unclear. Our data suggests that no common mtDNA mutation identifies metastatic cells; rather the metastatic potential of several ROS-generating mutations is largely determined by their mtDNA genomic landscapes, which can act either as an enhancer or repressor of metastasis...
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28347248/sirt3-functions-as-a-tumor-suppressor-in-hepatocellular-carcinoma
#16
Xianchun Zeng, Nanzhu Wang, Hui Zhai, Rongpin Wang, Jiahong Wu, Wei Pu
Hepatocellular carcinoma is one of the leading causes for cancer-related mortality worldwide. SIRT3 may function as either oncogene or tumor suppressor in a panel of cancers; however, the role of SIRT3 in hepatocellular carcinoma remains unclear. In this study, we assayed the expression level of SIRT3 in hepatocellular carcinoma tissues by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. A loss-of-function approach was used to examine the effects of SIRT3 on biological activity, including cell proliferative activity and invasive potential...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28339017/sirt1-is-required-for-mitochondrial-biogenesis-reprogramming-in-hypoxic-human-pulmonary-arteriolar-smooth-muscle-cells
#17
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
#18
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
#19
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
#20
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...
April 29, 2017: Biochemical and Biophysical Research Communications
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