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 (AU)