Published online Nov 21, 2013. doi: 10.3748/wjg.v19.i43.7594
Revised: September 16, 2013
Accepted: September 29, 2013
Published online: November 21, 2013
Ischemia-reperfusion injury (IRI) remains an unresolved and complicated situation in clinical practice, especially in the case of organ transplantation. Several factors contribute to its complexity; the depletion of energy during ischemia and the induction of oxidative stress during reperfusion initiate a cascade of pathways that lead to cell death and finally to severe organ injury. Recently, the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases has gained increasing attention from researchers, due to their involvement in the modulation of a wide variety of cellular functions. There are seven mammalian sirtuins and, among them, the nuclear/cytoplasmic sirtuin 1 (SIRT1) and the mitochondrial sirtuin 3 (SIRT3) are ubiquitously expressed in many tissue types. Sirtuins are known to play major roles in protecting against cellular stress and in controlling metabolic pathways, which are key processes during IRI. In this review, we mainly focus on SIRT1 and SIRT3 and examine their role in modulating pathways against energy depletion during ischemia and their involvement in oxidative stress, apoptosis, microcirculatory stress and inflammation during reperfusion. We present evidence of the beneficial effects of sirtuins against IRI and emphasize the importance of developing new strategies by enhancing their action.
Core tip: Sirtuins are responsible for the regulation of protein activation by deacetylating a range of proteins that play important roles in the pathophysiology of various diseases. The present review summarizes the beneficial effects of sirtuins 1 and 3, the two most prominent sirtuins involved in mammalian energy homeostasis and oxidative stress. We conclude that both sirtuins might be attractive targets for counteracting the detrimental effects of ischemia-reperfusion injury.