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https://www.readbyqxmd.com/read/28335087/ursolic-acid-and-mechanisms-of-actions-on-adipose-and-muscle-tissue-a-systematic-review
#1
REVIEW
Carlos K Katashima, Vagner R Silva, Tatyanne L Gomes, Claude Pichard, Gustavo D Pimentel
This systematic review aimed at addressing the ursolic acid actions as an adjunctive treatment of the obesity-mediated metabolic abnormalities. To explore our aims, we used the literature search including clinical and animal studies using the Medline and Google Scholar (up to December 2015). Out of 63 screened studies, 17 presented eligibility criteria, such as the use of ursolic acid on adiposity, energy expenditure and skeletal muscle mass in mice and humans. In the literature, we found that several physiological and molecular mechanisms are implicated in the effects of ursolic acid on obesity, energy expenditure, hepatic steatosis, skeletal muscle mass loss and physical fitness, such as (1) increase of thermogenesis by modulation adipocyte transcription factors, activation of 5' adenosine monophosphate-activated protein kinase and overexpression of the uncoupling protein 1 thermogenic marker; (2) enhancement of skeletal muscle mass by activation in bloodstream growth hormone and insulin-like growth factor-1 concentrations secretion, as well as in the activation of mammalian target of rapamycin and inhibition of ring-finger protein-1; and (3) improvement of physical fitness by skeletal muscle proliferator-activated receptor gamma co-activator alpha and sirtuin 1 expression...
March 23, 2017: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28334808/downregulation-of-pathways-implicated-in-liver-inflammation-and-tumorigenesis-of-glycogen-storage-disease-type-ia-mice-receiving-gene-therapy
#2
Goo-Young Kim, Joon Hyun Kwon, Jun-Ho Cho, Lisa Zhang, Brian C Mansfield, Janice Y Chou
Glycogen storage disease type Ia (GSD-Ia) is characterized by impaired glucose homeostasis and long-term risks of hepatocellular adenoma (HCA) and carcinoma (HCC). We have shown that the non-tumor-bearing (NT), recombinant adeno-associated virus (rAAV) vector-treated GSD-Ia mice (AAV-NT mice) expressing a wide range (0.9-63%) of normal hepatic glucose-6-phosphatase-α activity maintain glucose homeostasis and display physiologic features mimicking animals living under calorie restriction (CR). We now show that in AAV-NT mice, the signaling pathways of the CR mediators, AMP-activated protein kinase (AMPK) and sirtuin-1 are activated...
March 13, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28331525/the-anti-ageing-molecule-sirt1-mediates-beneficial-effects-of-cardiac-rehabilitation
#3
Giusy Russomanno, Graziamaria Corbi, Valentina Manzo, Nicola Ferrara, Giuseppe Rengo, Annibale A Puca, Salvatore Latte, Albino Carrizzo, Maria Consiglia Calabrese, Ramaroson Andriantsitohaina, Walter Filippelli, Carmine Vecchione, Amelia Filippelli, Valeria Conti
BACKGROUND: An exercise-based Cardiac Rehabilitation Programme (CRP) is established as adjuvant therapy in heart failure (HF), nevertheless it is underutilized, especially in the elderly. While the functional and hemodynamic effects of CRP are well known, its underlying molecular mechanisms have not been fully clarified. The present study aims to evaluate the effects of a well-structured 4-week CRP in patients with stable HF from a molecular point of view. RESULTS: A prospective longitudinal observational study was conducted on patients consecutively admitted to cardiac rehabilitation...
2017: Immunity & Ageing: I & A
https://www.readbyqxmd.com/read/28323907/resveratrol-inhibits-androgen-production-of-human-adrenocortical-h295r-cells-by-lowering-cyp17-and-cyp21-expression-and-activities
#4
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/28322251/modulation-of-central-carbon-metabolism-by-acetylation-of-isocitrate-lyase-in-mycobacterium-tuberculosis
#5
Jing Bi, Yihong Wang, Heguo Yu, Xiaoyan Qian, Honghai Wang, Jun Liu, Xuelian Zhang
Several enzymes involved in central carbon metabolism such as isocitrate lyase and phosphoenolpyruvate carboxykinase are key determinants of pathogenesis of Mycobacterium tuberculosis (M. tb). In this study, we found that lysine acetylation plays an important role in the modulation of central carbon metabolism in M. tb. Mutant of M. tb defective in sirtuin deacetylase exhibited improved growth in fatty acid-containing media. Global analysis of lysine acetylome of M. tb identified three acetylated lysine residues (K322, K331, and K392) of isocitrate lyase (ICL1)...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28306500/catching-sirtuin-2-intermediates-one-structure-at-the-time
#6
Schuyler Lee, Zhongzhou Chen, Gongyi Zhang
Sirtuins are a large enzyme family involved in installing and removing post-translational modifications involving lysine side chains. These enzymes have been of intense research interest and we now understand many details of their mechanism, although later steps of the deacetylase activity have remained a mystery. In this issue of Cell Chemical Biology, Wang et al. (2017) capture a late intermediate of SIRT2 catalysis and describe its structure.
March 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28303408/methylene-blue-decreases-mitochondrial-lysine-acetylation-in-the-diabetic-heart
#7
Jessica M Berthiaume, Chia-Heng Hsiung, Alison B Austin, Sean P McBrayer, Mikayla M Depuydt, Margaret P Chandler, Masaru Miyagi, Mariana G Rosca
Diabetic cardiomyopathy is preceded by mitochondrial alterations, and progresses to heart failure. We studied whether treatment with methylene blue (MB), a compound that was reported to serve as an alternate electron carrier within the mitochondrial electron transport chain (ETC), improves mitochondrial metabolism and cardiac function in type 1 diabetes. MB was administered at 10 mg/kg/day to control and diabetic rats. Both echocardiography and hemodynamic studies were performed to assess cardiac function...
March 16, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28295567/melatonin-reverses-h2-o2-induced-senescence-in-sh-sy5y-cells-by-enhancing-autophagy-via-sirtuin-1-deacetylation-of-the-rela-p65-subunit-of-nf-%C3%AE%C2%BAb
#8
Chutikorn Nopparat, Puritat Sinjanakhom, Piyarat Govitrapong
Autophagy, a degradation mechanism that plays a major role in maintaining cellular homeostasis and diminishes in aging, is considered an aging characteristic. Melatonin is an important hormone that plays a wide range of physiological functions, including the anti-aging effect, potentially via the regulation of the Sirtuin1 (SIRT1) pathway. The deacetylation ability of SIRT1 is important for controlling the function of several transcription factors, including nuclear factor kappa B (NF-ĸB). Apart from inflammation, NF-ĸB can regulate autophagy by inhibiting Beclin1, an initiator of autophagy...
March 14, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28292463/key-players-of-the-necroptosis-pathway-ripk1-and-sirt2-are-altered-in-placenta-from-preeclampsia-and-fetal-growth-restriction
#9
Natalie J Hannan, Sally Beard, Natalie K Binder, Kenji Onda, Tu'uhevaha J Kaitu'u-Lino, Qi Chen, Laura Tuohey, Manarangi De Silva, Stephen Tong
INTRODUCTION: Preeclampsia (PE) and fetal growth restriction (FGR) are among the leading causes of perinatal morbidity and mortality. Placental insufficiency is central to these conditions. The mechanisms underlying placental insufficiency are poorly understood. Apoptosis has long been considered the only form of regulated cell death, recent research has identified an alternate process of programmed cell death known as necroptosis [1]. Necroptosis is distinct from apoptosis, relying on the deacetylase sirtuin-2 [2], receptor interacting kinases RIPK1 and 3, and the pseudokinase MLKL [3]...
March 2017: Placenta
https://www.readbyqxmd.com/read/28287409/sirtuin-2-regulates-cellular-iron-homeostasis-via-deacetylation-of-transcription-factor-nrf2
#10
Xiaoyan Yang, Seong-Hoon Park, Hsiang-Chun Chang, Jason S Shapiro, Athanassios Vassilopoulos, Konrad T Sawicki, Chunlei Chen, Meng Shang, Paul W Burridge, Conrad L Epting, Lisa D Wilsbacher, Supak Jenkitkasemwong, Mitchell Knutson, David Gius, Hossein Ardehali
SIRT2 is a cytoplasmic sirtuin that plays a role in various cellular processes, including tumorigenesis, metabolism, and inflammation. Since these processes require iron, we hypothesized that SIRT2 directly regulates cellular iron homeostasis. Here, we have demonstrated that SIRT2 depletion results in a decrease in cellular iron levels both in vitro and in vivo. Mechanistically, we determined that SIRT2 maintains cellular iron levels by binding to and deacetylating nuclear factor erythroid-derived 2-related factor 2 (NRF2) on lysines 506 and 508, leading to a reduction in total and nuclear NRF2 levels...
March 13, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28286128/deacylation-mechanism-by-sirt2-revealed-in-the-1-sh-2-o-myristoyl-intermediate-structure
#11
Yi Wang, Yi Man Eva Fung, Weizhe Zhang, Bin He, Matthew Wai Heng Chung, Jing Jin, Jing Hu, Hening Lin, Quan Hao
Sirtuins are NAD-dependent deacylases. Previous studies have established two important enzymatic intermediates in sirtuin-catalyzed deacylation, an alkylamidate intermediate I, which is then converted to a bicyclic intermediate II. However, how intermediate II is converted to products is unknown. Based on potent SIRT2-specific inhibitors we developed, here we report crystal structures of SIRT2 in complexes with a thiomyristoyl lysine peptide-based inhibitor and carba-NAD or NAD. Interestingly, by soaking crystals with NAD, we capture a distinct covalent catalytic intermediate (III) that is different from the previously established intermediates I and II...
March 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28285806/mitochondrial-sirtuins-and-molecular-mechanisms-of-aging
#12
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/28279944/adipose-tissue-nad-homeostasis-sirtuins-and-poly-adp-ribose-polymerases-important-players-in-mitochondrial-metabolism-and-metabolic-health
#13
REVIEW
Riikka Jokinen, Sini Pirnes-Karhu, Kirsi H Pietiläinen, Eija Pirinen
Obesity, a chronic state of energy overload, is characterized by adipose tissue dysfunction that is considered to be the major driver for obesity associated metabolic complications. The reasons for adipose tissue dysfunction are incompletely understood, but one potential contributing factor is adipose tissue mitochondrial dysfunction. Derangements of adipose tissue mitochondrial biogenesis and pathways associate with obesity and metabolic diseases. Mitochondria are central organelles in energy metabolism through their role in energy derivation through catabolic oxidative reactions...
February 27, 2017: Redox Biology
https://www.readbyqxmd.com/read/28273448/mutations-that-allow-sir2-orthologs-to-function-in-a-nad-depleted-environment
#14
Caitlin R Ondracek, Vincent Frappier, Alison E Ringel, Cynthia Wolberger, Leonard Guarente
Sirtuin enzymes depend on NAD(+) to catalyze protein deacetylation. Therefore, the lowering of NAD(+) during aging leads to decreased sirtuin activity and may speed up aging processes in laboratory animals and humans. In this study, we used a genetic screen to identify two mutations in the catalytic domain of yeast Sir2 that allow the enzyme to function in an NAD(+)-depleted environment. These mutant enzymes give rise to a significant increase of yeast replicative lifespan and increase deacetylation by the Sir2 ortholog, SIRT1, in mammalian cells...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28264931/key-proteins-and-pathways-that-regulate-lifespan
#15
Haihui Pan, Toren Finkel
Here, we review three sets of key proteins and their corresponding downstream pathways that have been linked to extending lifespan and promoting health span in a wide range of organisms. In particular, we review the biology of the sirtuin family of proteins, the Insulin/Insulin-like Growth Factor (IGF) signaling (IIS) pathway, and the mechanistic Target of Rapamycin (mTOR). Using insights derived from simple model organisms, mice and humans we discuss how these proteins and pathways may potentially alter the rate of aging...
March 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28258519/sirtuins-a-promising-target-in-slowing-down-the-ageing-process
#16
REVIEW
Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska
Ageing is a plastic process and can be successfully modulated by some biomedical approaches or pharmaceutics. In this manner it is possible to delay or even prevent some age-related pathologies. There are some defined interventions, which give promising results in animal models or even in human studies, resulting in lifespan elongation or healthspan improvement. One of the most promising targets for anti-ageing approaches are proteins belonging to the sirtuin family. Sirtuins were originally discovered as transcription repressors in yeast, however, nowadays they are known to occur in bacteria and eukaryotes (including mammals)...
March 3, 2017: Biogerontology
https://www.readbyqxmd.com/read/28258190/sirt3-deficiency-promotes-lung-fibrosis-by-augmenting-alveolar-epithelial-cell-mitochondrial-dna-damage-and-apoptosis
#17
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/28257421/the-mechanism-of-sirtuin-2-mediated-exacerbation-of-alpha-synuclein-toxicity-in-models-of-parkinson-disease
#18
Rita Machado de Oliveira, Hugo Vicente Miranda, Laetitia Francelle, Raquel Pinho, Éva M Szegö, Renato Martinho, Francesca Munari, Diana F Lázaro, Sébastien Moniot, Patrícia Guerreiro, Luis Fonseca, Zrinka Marijanovic, Pedro Antas, Ellen Gerhardt, Francisco Javier Enguita, Bruno Fauvet, Deborah Penque, Teresa Faria Pais, Qiang Tong, Stefan Becker, Sebastian Kügler, Hilal Ahmed Lashuel, Clemens Steegborn, Markus Zweckstetter, Tiago Fleming Outeiro
Sirtuin genes have been associated with aging and are known to affect multiple cellular pathways. Sirtuin 2 was previously shown to modulate proteotoxicity associated with age-associated neurodegenerative disorders such as Alzheimer and Parkinson disease (PD). However, the precise molecular mechanisms involved remain unclear. Here, we provide mechanistic insight into the interplay between sirtuin 2 and α-synuclein, the major component of the pathognomonic protein inclusions in PD and other synucleinopathies...
March 2017: PLoS Biology
https://www.readbyqxmd.com/read/28256782/characterization-of-lysine-acetylation-of-a-phosphoenolpyruvate-carboxylase-involved-in-glutamate-overproduction-in-corynebacterium-glutamicum
#19
Megumi Nagano-Shoji, Yuma Hamamoto, Yuta Mizuno, Ayuka Yamada, Masaki Kikuchi, Mikako Shirouzu, Takashi Umehara, Minoru Yoshida, Makoto Nishiyama, Saori Kosono
Protein Nε-acylation is emerging as a ubiquitous post-translational modification. In Corynebacterium glutamicum, which is utilized for industrial production of L-glutamate, the levels of protein acetylation and succinylation change drastically under the conditions that induce glutamate overproduction. Here, we characterized the acylation of phosphoenolpyruvate carboxylase (PEPC), an anaplerotic enzyme that supplies oxaloacetate for glutamate overproduction. We showed that acetylation of PEPC at lysine 653 decreased enzymatic activity, leading to reduced glutamate production...
March 3, 2017: Molecular Microbiology
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
#20
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
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