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Sirt3 AND metformin

Yao Wu, Wei-Nan Gao, Ya-Nan Xue, Li-Chao Zhang, Juan-Juan Zhang, Sheng-Yao Lu, Xiao-Yu Yan, Hui-Mei Yu, Jing Su, Lian-Kun Sun
Increasing evidence suggests that mitochondrial respiratory chain complex I participates in carcinogenesis and cancer progression by providing energy and maintaining mitochondrial function. However, the role of complex I in ovarian cancer is largely unknown. In this study we showed that metformin, considered to be an inhibitor of complex I, simultaneously inhibited cell growth and induced mitochondrial-related apoptosis in human ovarian cancer cells. Metformin interrupted cellular energy metabolism mainly by causing damage to complex I that impacted mitochondrial function...
June 15, 2018: Experimental Cell Research
Santosh Karnewar, Praveen Kumar Neeli, Devayani Panuganti, Sasikumar Kotagiri, Sreevidya Mallappa, Nishant Jain, Mahesh Kumar Jerald, Srigiridhar Kotamraju
Endothelial senescence in conjunction with mitochondrial dysfunction orchestrates age-associated cardiovascular disorders. In this study we investigated the causal link between these two processes and studied the molecular mechanisms by which metformin acts to coordinate the delay of endothelial senescence via enhancing mitochondrial biogenesis/function. AMPK activators metformin and AICAR delayed endothelial senescence via SIRT1-mediated upregulation of DOT1L, leading to increased trimethylation of H3K79 (H3K79me3)...
April 2018: Biochimica et Biophysica Acta
Bożena Sosnowska, Mohsen Mazidi, Peter Penson, Anna Gluba-Brzózka, Jacek Rysz, Maciej Banach
The sirtuins, silent mating-type information regulation 2 (SIRTs), are a family of nicotinamide adenine dinucleotide (NAD+ )-dependent histone deacetylases with important roles in regulating energy metabolism and senescence. Activation of SIRTs appears to have beneficial effects on lipid metabolism and antioxidants, prompting investigation of the roles of these proteins in atherogenesis. Although clinical data are currently limited, the availability and safety of SIRT activators such as metformin and resveratrol provide an excellent opportunity to conduct research to better understand the role of SIRTs in human atherosclerosis...
October 2017: Atherosclerosis
Jamie L Barger, James M Vann, Nicole L Cray, Thomas D Pugh, Angela Mastaloudis, Shelly N Hester, Steven M Wood, Michael A Newton, Richard Weindruch, Tomas A Prolla
Caloric restriction (CR) without malnutrition has been shown to retard several aspects of the aging process and to extend lifespan in different species. There is strong interest in the identification of CR mimetics (CRMs), compounds that mimic the beneficial effects of CR on lifespan and healthspan without restriction of energy intake. Identification of CRMs in mammals is currently inefficient due to the lack of screening tools. We have performed whole-genome transcriptional profiling of CR in seven mouse strains (C3H/HeJ, CBA/J, DBA/2J, B6C3F1/J, 129S1/SvImJ, C57BL/6J, and BALB/cJ) in white adipose tissue (WAT), gastrocnemius muscle, heart, and brain neocortex...
August 2017: Aging Cell
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...
August 30, 2017: Gene
Noelia Diaz-Morales, Susana Rovira-Llopis, Celia Bañuls, Sandra Lopez-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 at studying its effect on reactive oxygen species (ROS) production, antioxidant enzyme 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 1700 mg per day), and in 40 sex- and age-matched control subjects. 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, whereas metformin was shown to revert these effects...
December 10, 2017: Antioxidants & Redox Signaling
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
Xiao-Yu Cheng, Yang-Yang Li, Cheng Huang, Jun Li, Hong-Wei Yao
Current drug therapy fails to reduce lung destruction of chronic obstructive pulmonary disease (COPD). AMP-activated protein kinase (AMPK) has emerged as an important integrator of signals that control energy balance and lipid metabolism. However, there are no studies regarding the role of AMPK in reducing inflammatory responses and cellular senescence during the development of emphysema. Therefore, we hypothesize that AMPK reduces inflammatroy responses, senescence, and lung injury. To test this hypothesis, human bronchial epithelial cells (BEAS-2B) and small airway epithelial cells (SAECs) were treated with cigarette smoke extract (CSE) in the presence of a specific AMPK activator (AICAR, 1 mM) and inhibitor (Compound C, 5 μM)...
April 4, 2017: Oncotarget
Yen-Chun Lai, Diana M Tabima, John J Dube, Kara S Hughan, Rebecca R Vanderpool, Dmitry A Goncharov, Claudette M St Croix, Adolfo Garcia-Ocaña, Elena A Goncharova, Stevan P Tofovic, Ana L Mora, Mark T Gladwin
BACKGROUND: Pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF) is an increasingly recognized clinical complication of metabolic syndrome. No adequate animal model of PH-HFpEF is available, and no effective therapies have been identified to date. A recent study suggested that dietary nitrate improves insulin resistance in endothelial nitric oxide synthase null mice, and multiple studies have reported that both nitrate and its active metabolite, nitrite, have therapeutic activity in preclinical models of pulmonary hypertension...
February 23, 2016: Circulation
Yuping Song, Jingli Shi, Ying Wu, Chong Han, Junjie Zou, Yongquan Shi, Zhimin Liu
BACKGROUND: SIRT3 is an important regulator in cell metabolism, and recent studies have shown that it may be involved in the pharmacological effects of metformin. However, the molecular mechanisms underlying this process are unclear. METHODS: The effects of SIRT3 on the regulation of oxidative stress and insulin resistance in skeletal muscle were evaluated in vitro. Differentiated L6 skeletal muscle cells were treated with 750 µmol/L palmitic acid to induce insulin resistance...
2014: Chinese Medical Journal
Marcin Buler, Sanna-Mari Aatsinki, Valerio Izzi, Johanna Uusimaa, Jukka Hakkola
The sirtuins (SIRTs; SIRT1-7) are a family of NAD(+)-dependent enzymes that dynamically regulate cellular physiology. Apart from SIRT1, the functions and regulatory mechanisms of the SIRTs are poorly defined. We explored regulation of the SIRT family by 2 energy metabolism-controlling factors: peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) and AMP-activated protein kinase (AMPK). Overexpression of PGC-1α in mouse primary hepatocytes increased SIRT5 mRNA expression 4-fold and also the protein in a peroxisome proliferator-activated receptor α (PPARα)- and estrogen-related receptor α (ERRα)-dependent manner...
July 2014: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Marcin Buler, Sanna-Mari Aatsinki, Valerio Izzi, Jukka Hakkola
Metformin inhibits ATP production in mitochondria and this may be involved in the anti-hyperglycemic effects of the drug. Sirtuin 3 (SIRT3) is a mitochondrial protein deacetylase that regulates the function of the electron transport chain and maintains basal ATP yield. We hypothesized that metformin treatment could diminish mitochondrial ATP production through downregulation of SIRT3 expression. Glucagon and cAMP induced SIRT3 mRNA in mouse primary hepatocytes. Metformin prevented SIRT3 induction by glucagon...
2012: PloS One
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