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https://www.readbyqxmd.com/read/28542596/progressive-mitochondrial-protein-lysine-acetylation-and-heart-failure-in-a-model-of-friedreich-s-ataxia-cardiomyopathy
#1
Amanda R Stram, Gregory R Wagner, Brian D Fogler, P Melanie Pride, Matthew D Hirschey, R Mark Payne
INTRODUCTION: The childhood heart disease of Friedreich's Ataxia (FRDA) is characterized by hypertrophy and failure. It is caused by loss of frataxin (FXN), a mitochondrial protein involved in energy homeostasis. FRDA model hearts have increased mitochondrial protein acetylation and impaired sirtuin 3 (SIRT3) deacetylase activity. Protein acetylation is an important regulator of cardiac metabolism and loss of SIRT3 increases susceptibility of the heart to stress-induced cardiac hypertrophy and ischemic injury...
2017: PloS One
https://www.readbyqxmd.com/read/28536275/sirt3-mediated-dimerization-of-idh2-directs-cancer-cell-metabolism-and-tumor-growth
#2
Xianghui Zou, Yueming Zhu, Seong-Hoon Park, Guoxiang Liu, Joseph O'Brien, Haiyan Jiang, David Gius
The isocitrate dehydrogenase IDH2 produces α-ketoglutarate by oxidizing isocitrate, linking glucose metabolism to oxidative phosphorylation. In this study, we report that loss of SIRT3 increases acetylation of IDH2 at lysine 413 (IDH2-K413-Ac), thereby decreasing its enzymatic activity by reducing IDH2 dimer formation. Expressing a genetic acetylation mimetic IDH2 mutant (IDH2(K413Q)) in cancer cells decreased IDH2 dimerization and enzymatic activity and increased cellular reactive oxygen species (ROS) and glycolysis, suggesting a shift in mitochondrial metabolism...
May 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28526626/longevity-and-healthy-ageing-genes-foxo3a-and-sirt3-serum-protein-marker-and-new-road-map-to-burst-oxidative-stress-by-withania-somnifera
#3
Rashmita Pradhan, Rahul Kumar, Shashank Shekhar, Nitish Rai, Akash Ambashtha, Joyita Banerjee, Mona Pathak, S N Dwivedi, Sharmistha Dey, Aparajit B Dey
BACKGROUND: Ageing process is characterized by a decline in function; different age related diseases and excessive age associated mortality. There has always been a quest for easily accessible biomarkers to monitor and identify the development of age-associated stress for providing new anti-ageing strategies. Forkhead box protein O3A (FOXO3A) and Sirtuin3 (SIRT3) are such potential markers which plays important role in a wide variety of cellular mechanisms and has been proposed to be an ideal candidate to study longevity and are potential candidate for healthy ageing by oxidative burst...
May 16, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28520180/sirt3-as-a-regulator-of-hepatic-autophagy
#4
EDITORIAL
Chun-Seok Cho, David B Lombard, Jun Hee Lee
No abstract text is available yet for this article.
May 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28514599/a-bioenergetics-systems-evaluation-of-ketogenic-diet-liver-effects
#5
Lewis J Hutfles, Heather M Wilkins, Scott J Koppel, Ian W Weidling, J Eva Selfridge, Eephie Tan, John P Thyfault, Chad Slawson, Aron W Fenton, Hao Zhu, Russell H Swerdlow
Ketogenic diets induce hepatocyte fatty acid oxidation and ketone body production. To further evaluate how ketogenic diets affect hepatocyte bioenergetic infrastructure, we analyzed livers from C57Bl/6J male mice maintained for one month on a ketogenic or standard chow diet. Compared to the standard diet, the ketogenic diet increased cytosolic and mitochondrial protein acetylation and also altered protein succinylation patterns. SIRT3 protein decreased while SIRT5 protein increased, and gluconeogenesis, oxidative phosphorylation, and mitochondrial biogenesis pathway proteins were variably and likely strategically altered...
May 17, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28512002/cell-surface-g-protein-coupled-receptors-for-tumor-associated-metabolites-a-direct-link-to-mitochondrial-dysfunction-in-cancer
#6
REVIEW
Bojana Ristic, Yangzom D Bhutia, Vadivel Ganapathy
Mitochondria are the sites of pyruvate oxidation, citric acid cycle, oxidative phosphorylation, ketogenesis, and fatty acid oxidation. Attenuation of mitochondrial function is one of the most significant changes that occurs in tumor cells, directly linked to oncogenesis, angiogenesis, Warburg effect, and epigenetics. In particular, three mitochondrial enzymes are inactivated in cancer: pyruvate dehydrogenase (PDH), succinate dehydrogenase (SDH), and 3-hydroxy-3-methylglutaryl CoA synthase-2 (HMGCS2). These enzymes are subject to regulation via acetylation/deacetylation...
May 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28506746/the-nad-dependent-deacetylase-bifidobacterium-longum-sir2-in-response-to-oxidative-stress-by-deacetylating-foxo3a-and-sigh-%C3%AF-h-in-bifidobacterium-longum-and-hek293t-cells-respectively
#7
Qing Guo, Shiyu Li, Yajie Xie, Qian Zhang, Mengge Liu, Zhenrui Xu, Hanxiao Sun, Yan Yang
Silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation. The mammalian sirtuin family SIRT1, SIRT2, SIRT3 and SIRT6 can regulate oxidative stress. The probiotics (Bifidobacterium longum(B.longum) and Lactobacillus acidophilus(L. acidophilus)) have Sir2 gene family and have antioxidant activity in human body. it remains unknown whether probiotics Sir2 has a direct role in regulating oxidative stress. To this end, we knockout BL-sir2(sir2 B. longum) and LA-sir2(sir2 L...
May 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28503736/hydrogen-sulfide-pretreatment-improves-mitochondrial-function-in-myocardial-hypertrophy-via-a-sirt3-dependent-manner
#8
Guoliang Meng, Jieqiong Liu, Shangmin Liu, Qiuyi Song, Lulu Liu, Liping Xie, Yi Han, Yong Ji
BACKGROUND AND PURPOSE Hydrogen sulfide (H2 S) is a gaseous signal molecule with anti-oxidative ability. Sirtuin 3 (SIRT3) is closely associated with mitochondrial function and oxidative stress. The study was to investigate whether and how H2 S improved myocardial hypertrophy via a SIRT3-dependent manner. EXPERIMENTAL APPROACH Neonatal rat cardiomyocytes were pre-treated with NaHS (50 μM) for 4 h followed by angiotensin II (Ang II, 100 nM) for 24 h. SIRT3 was silenced with siRNA technology. SIRT 3 promoter activity and expression, cell surface, hypertrophic gene mRNA expression, mitochondrial oxygen consumption rate and membrane potential were measured...
May 15, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28500761/melatonin-ameliorates-myocardial-ischemia-reperfusion-injury-through-sirt3-dependent-regulation-of-oxidative-stress-and-apoptosis
#9
Mengen Zhai, Buying Li, Weixun Duan, Lin Jing, Bin Zhang, Meng Zhang, Liming Yu, Zhenhua Liu, Bo Yu, Kai Ren, Erhe Gao, Yang Yang, Hongliang Liang, Zhenxiao Jin, Shiqiang Yu
Sirtuins are a family of highly evolutionarily conserved nicotinamide adenine nucleotide-dependent histone deacetylases. Sirtuin-3 (SIRT3) is a member of the sirtuin family that is localized primarily to the mitochondria and protects against oxidative stress-related diseases, including myocardial ischemia/reperfusion (MI/R) injury. Melatonin has a favorable effect in ameliorating MI/R injury. We hypothesized that melatonin protects against MI/R injury by activating the SIRT3 signaling pathway. In this study, mice were pre-treated with or without a selective SIRT3 inhibitor and then subjected to MI/R operation...
May 13, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28499942/metformin-ameliorates-hypoxia-reoxygenation-induced-cardiomyocyte-apoptosis-based-on-the-sirt3-signaling-pathway
#10
Yanyan Du, Jingjing Zhang, Fang Fang, Xiqing Wei, Hongsheng Zhang, Hongyong Tan, Jinguo Zhang
Myocardial hypoxia/reoxygenation (H/R) injury is one of the main causes of death and disability worldwide. However, a limited number of therapies are available to minimize the detrimental effects of this injury. Recently, researchers have demonstrated that metformin exerts direct cardioprotective effects against H/R. The aim of this study was to investigate the underlying mechanisms of how metformin affects myocardial hypoxia/reoxygenation (H/R) injury. In our study, the activities of lactate dehydrogenase (LDH) and superoxide dismutase (SOD) as well as the levels of malondialdehyde (MDA) were measured...
May 9, 2017: Gene
https://www.readbyqxmd.com/read/28480597/melatonin-protects-against-diabetic-cardiomyopathy-through-mst1-sirt3-signaling
#11
Mingming Zhang, Jie Lin, Shanjie Wang, Zheng Cheng, Jianqiang Hu, Tingting Wang, Wanrong Man, Tao Yin, Wenyi Guo, Erhe Gao, Russel J Reiter, Haichang Wang, Dongdong Sun
The present study investigated the effects of melatonin on diabetic cardiomyopathy (DCM) and determined the underlying mechanisms. Echocardiography indicated that melatonin notably mitigated the adverse left ventricle remodeling and alleviated cardiac dysfunction in DCM. The mechanisms were attributed to increased autophagy, reduced apoptosis and alleviated mitochondrial dysfunction. Furthermore, melatonin inhibited Mst1 phosphorylation and promoted Sirt3 expression in DCM. These results indicated that melatonin may exert its effects through Mst1/ Sirt3 signaling...
May 8, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28467723/does-metformin-protect-diabetic-patients-from-oxidative-stress-and-leukocyte-endothelium-interactions
#12
Noelia Diaz-Morales, Susana Rovira-Llopis, Celia Bañuls, Sandra López-Domenech, Irene Escribano-Lopez, Silvia Veses, Ana Jover, Milagros Rocha, Antonio Hernandez-Mijares, Victor M Victor
Since metformin can exert beneficial vascular effects, we aimed to study its effect on reactive oxygen species (ROS) production, antioxidant enzymes expression, levels of adhesion molecules, and leukocyte-endothelium interactions in the leukocytes from type 2 diabetic (T2D) patients. The study was carried out in 72 T2D patients (41 of whom were treated with metformin for at least 12 months at a dose of 1700mg per day), and 40 sex- and age-matched control subjects. Whereas leukocytes from T2D patients exhibited enhanced levels of mitochondrial ROS and decreased mRNA levels of glutathione peroxidase 1 (gpx1) and sirtuin 3 (sirt3) with respect to controls, metformin was shown to revert these effects...
May 3, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28465484/sirt3-klf15-signaling-ameliorates-kidney-injury-induced-by-hypertension
#13
Na Li, Jie Zhang, Xuefang Yan, Chen Zhang, Hui Liu, Xiaolan Shan, Jingyuan Li, Yi Yang, Chengmin Huang, Peng Zhang, Yun Zhang, Peili Bu
Renal fibrosis participates in the progression of hypertension-induced kidney injury. The effect of SIRT3, a member of the NAD+-dependent deacetylase family, in hypertensive nephropathy remains unclear. In this study, we found that SIRT3 was reduced after angiotensin II (AngII) treatment both in vivo and in vitro. Furthermore, SIRT3-knockout mice aggravated hypertension-induced renal dysfunction and renal fibrosis via chronic AngII infusion (2000 ng/kg per minute for 42 days). On the contrary, SIRT3-overexpression mice attenuated AngII-induced kidney injury compared with wild-type mice...
April 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28459202/estradiol-via-estrogen-receptor-beta-influences-ros-levels-through-the-transcriptional-regulation-of-sirt3-in-human-seminoma-tcam-2-cells
#14
Salvatore Panza, Marta Santoro, Francesca De Amicis, Catia Morelli, Valentina Passarelli, Patrizia D'Aquila, Francesca Giordano, Erika Cione, Giuseppe Passarino, Dina Bellizzi, Saveria Aquila
Human testis, gonocytes, and adult germ cells mainly express estrogen receptor beta, and estrogen receptor beta loss is associated with advanced tumor stage; however, the molecular mechanisms of estrogen receptor beta-protective effects are still to be defined. Herein, we provide evidence that in human seminoma TCam-2 cells, E2 through estrogen receptor beta upregulates the mitochondrial deacetylase sirtuin-3 at protein and messenger RNA levels. Specifically, E2 increases sirtuin-3 expression through a transcriptional mechanism due to the occupancy of sirtuin-3 promoter by estrogen receptor beta, together with the transcription factor Sp1 as evidenced by Chip reChIp assay...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28449871/sirt3-and-mitochondrial-metabolism-in-neurodegenerative-diseases
#15
REVIEW
Illari Salvatori, Cristiana Valle, Alberto Ferri, Maria Teresa Carrì
The NAD(+)-dependent deacetylase protein Sirtuin 3 (SIRT3) is emerging among the factors playing a key role in the regulation of mitochondrial function and in the prevention of oxidative stress. This deacetylase activates protein substrates directly involved in the production and detoxification of ROS, such as superoxide dismutase 2 and catalase, but also enzymes in the lipid beta-oxidation pathway. In this paper we review existing evidence on the role of SIRT3 in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington disease, including data from new experiments in a model for amyotrophic lateral sclerosis linked to mutations in superoxide dismutase 1...
April 25, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28443025/honokiol-induces-apoptosis-g1-arrest-and-autophagy-in-kras-mutant-lung-cancer-cells
#16
Lian-Xiang Luo, Ying Li, Zhong-Qiu Liu, Xing-Xing Fan, Fu-Gang Duan, Run-Ze Li, Xiao-Jun Yao, Elaine Lai-Han Leung, Liang Liu
Aberrant signaling transduction induced by mutant KRAS proteins occurs in 20∼30% of non-small cell lung cancer (NSCLC), however, a direct and effective pharmacological inhibitor targeting KRAS has not yet reached the clinic to date. Honokiol, a small molecular polyphenol natural biophenolic compound derived from the bark of magnolia trees, exerts anticancer activity, however, its mechanism remains unknown. In this study, we sought to investigate the in vitro effects of honokiol on NSCLC cell lines harboring KRAS mutations...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28437863/sirt3-acts-as-a-negative-regulator-of-autophagy-dictating-hepatocyte-susceptibility-to-lipotoxicity
#17
Songtao Li, Xiaobing Dou, Hua Ning, Qing Song, Wei Wei, Ximei Zhang, Chen Shen, Jiaxin Li, Changhao Sun, Zhenyuan Song
Lipotoxicity induced by saturated fatty acids (SFAs) plays a central role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD); however, the exact mechanism(s) remain to be fully elucidated. SIRT3 is an NAD(+) -dependent deacetylase primarily located inside mitochondria. In this study, we demonstrated that a SFAs-rich high-fat diet (HFD) was more detrimental to the liver than an isocaloric unsaturated FAs-rich HFD. Unexpectedly, SIRT3 expression/activity were significantly elevated in the livers of mice exposed to the SFAs-rich HFD...
April 24, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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
#18
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 20, 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
#19
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
#20
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...
May 23, 2017: Oncotarget
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