Nephroprotective action of sirtuin 1 (SIRT1)

Abstract

Sirtuins, silent information regulator 2 (Sir 2) proteins, belong to the family of NAD(+)-dependent enzymes with deacetylase or mono-ADP-ribosyltransferase activity. These enzymes are responsible for processes of DNA repair or recombination, chromosomal stability and gene transcription. In mammals, sirtuins occur in seven varieties, from 1 to 7 (SIRT1-SIRT7), differing among themselves with location. SIRT1, the best known variety, exerts its effects on proteins via NAD(+) coenzymes, being thus associated with cellular energetic metabolism and the 'red-ox' state. Its deficits are, among others, concomitant with stressful situations and associated with pathophysiologies of many medical conditions, including diabetes mellitus, cardiovascular diseases, neurodegenerative syndromes and kidney diseases. In kidney disorders, it promotes (stimulates) the survival of cells in an affected kidney by modulating their responses to various stress stimuli, takes part in arterial blood pressure control, protects against cellular apoptosis in renal tubules by catalase induction and triggers autophagy. More and more available in vitro and in vivo data indicate SIRT1 activity to be oriented, among others, towards nephroprotection. Thus, SIRT1 may become a novel element in the therapy of age-related renal diseases, including diabetic nephropathy.

Sirtuins as novel players in the pathogenesis of diabetes mellitus

“…In addition, SIRT1 was found to be closely associated with the survival of cells in an affected kidney by modulating their responses to various stress stimuli, SIRT1 also takes part in arterial blood pressure control, protects against cellular apoptosis in renal tubules by inducing catalase and triggers autophagy. Hence, activation of SIRT1 may become a novel target in the treatment of diabetic nephropathy [66] . Niacin (vitamin B3), is also an important intermediate for the biosynthesis of NAD + that can used for the activation of SIRT1 [67] .…”

Olmesartan Prevents Microalbuminuria in db/db Diabetic Mice Through Inhibition of Angiotensin II/p38/SIRT1-Induced Podocyte Apoptosis

“…The NAD + -dependent deacetylase Silent mating type information regulation 1 (SIRT1) is implicated in the pathogenesis of various diseases, including renal diseases [8,9]. Thus, it has been shown that activation of Adenosine 5'-monophosphate-activated protein kinase (AMPK) by resveratrol decreased albuminuria in diabetic mice through SIRT1 [10].…”

Endogenous factors and mechanisms of renoprotection and renal repair

“…30 Resveratrol is a natural compound capable of activating NRF2 and might thus depict another treatment option to counterbalance kidney damage. 32 SIRT1 protects against apoptosis via activation of catalase with a number of publications reporting about its nephroprotective effect making it another promising therapy target in the area of kidney disease and diabetes mellitus.…”