Role of Silent Information Regulator 1 ( SIRT1 ) in Regulating Oxidative Stress and Inflammation
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REVIEW
Role of Silent Information Regulator 1 (SIRT1) in Regulating Oxidative Stress and Inflammation Vivek Singh1 and Saba Ubaid
1,2
Silent information regulator 1 (SIRT1) is a ubiquitously expressed protein and has an intricate role in the pathology, progression, and treatment of several diseases. SIRT1 is a NAD+-dependent deacetylase and regulates gene expression by histone deacetylation. Deletion of SIRT1 in the liver, pancreas, and brain significantly increases the reactive oxygen species (ROS) and inflammatory response. Literature survey on SIRT1 shows the evidence for its role in preventing oxidative stress and inflammation. Oxidative stress and inflammation are closely related pathophysiological processes and are involved in the pathogenesis of a number of chronic disorders such as fatty liver diseases, diabetes, and neurodegenerative diseases. Both oxidative stress and inflammation alter the expression of several genes such as nuclear factor E2 related factor (Nrf2), nuclear factor E2 related factor 2 (Nef2), nuclear factor kappa B (NF-kB), pancreatic and duodenal homeobox factor 1 (PDX1), interleukin-1 (IL1), forkhead box class O (FOXO), and tumour necrosis factor alpha (TNF-α). By annotating this knowledge, we can conclude that modulating the expression of SIRT1 might prevent the onset of diseases inexorably linked to the liver, pancreas, and brain. Abstract—
KEY WORDS: oxidative stress; inflammation; SIRT1; liver; pancreas; brain.
INTRODUCTION Histone deacetylases (HDACs) are a group of enzymes that catalyzes the removal of acetyl group from
Highlights • Oxidative stress and inflammation are the leading cause of certain disease. • SIRT1 is involved in regulation of ROS and inflammation through epigenetic modification of several genes. • Therapeutic intervention against SIRT1 may open a new gate for the treatment of many diseases. 1
Department of Biochemistry, King George’s Medical University (KGMU), Lucknow, U.P. 226003, India 2 To whom correspondence should be addressed at Department of Biochemistry, King George’s Medical University (KGMU), Lucknow, U.P. 226003, India. E-mail: [email protected]
ε-N-acetyl lysine amino acid residues from histones and non-histone proteins. To date, 18 different HDACs have been identified in humans. HDACs are grouped into 2 families (‘classical’ and ‘sirtuins’) and 4 classes (class I, class II, class III, class IV) based on their sequence homology to yeast HDACs and the mechanism of action [1]. Sirtuins are highly conserved NAD-dependent class III histone deacetylase which shows high sequence similarity to yeast Saccharomyces cerevisiae protein sir2 (silent information regulator 2) and shows no sequence resemblance to the classical family of HDACs [2]. Seven sirtuin isoforms—SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6, and SIRT7—have been identified in humans [3]. They contain a conserved catalytic core domain composed of approximately 275 amino acid residues with variable N- and Ctermini. Except SIRT1 which is ubiquitously expressed,
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