title: Sirtuin and metabolic kidney disease.
abstract: Sirtuin is a nicotinamide adenine dinucleotide-dependent deacetylase. One of its isoforms, Sirt1, is a key molecule in glucose, lipid, and energy metabolism. The renal protective effects of Sirt1 are found in various models of renal disorders with metabolic impairment, such as diabetic nephropathy. Protective effects include the maintenance of glomerular barrier function, anti-fibrosis effects, anti-oxidative stress effects, and regulation of mitochondria function and energy metabolism. Various target molecules subject to direct deacetylation or epigenetic gene regulation have been identified as effectors of the renal protective function of sirtuin. Recently, it was demonstrated that Sirt1 expression decreases in proximal tubules before albuminuria in a mouse model of diabetic nephropathy, and that albuminuria is suppressed in proximal tubule-specific mice overexpressing Sirt1. These findings suggest that decreased Sirt1 expression in proximal tubular cells causes abnormal nicotine metabolism and reduces the supply of nicotinamide mononucleotide from renal tubules to glomeruli. This further decreases expression of Sirt1 in glomerular podocytes and increases expression of a tight junction protein, claudin-1, which results in albuminuria. Activators of the sirtuin family of proteins, including resveratrol, may be important in the development of new therapeutic strategies for treating metabolic kidney diseases, including diabetic nephropathy.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Wakino
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
mesh_terms: D000818:Animals; D015195:Drug Design; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000627:therapeutic use; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D058990:Molecular Targeted Therapy; D009243:NAD / Q000378:metabolism*; D015398:Signal Transduction; D037761:Sirtuins / Q000378:metabolism*
chemical_list: D020536:Enzyme Activators; D009243:NAD; D037761:Sirtuins