title: Pathways for ischemic cytoprotection: role of sirtuins in caloric restriction, resveratrol, and ischemic preconditioning.
abstract: Caloric restriction (CR), resveratrol, and ischemic preconditioning (IPC) have been shown to promote protection against ischemic injury in the heart and brain, as well as in other tissues. The activity of sirtuins, which are enzymes that modulate diverse biologic processes, seems to be vital in the ability of these therapeutic modalities to prevent against cellular dysfunction and death. The protective mechanisms of the yeast Sir2 and the mammalian homolog sirtuin 1 have been extensively studied, but the involvement of other sirtuins in ischemic protection is not yet clear. We examine the roles of mammalian sirtuins in modulating protective pathways against oxidative stress, energy depletion, excitotoxicity, inflammation, DNA damage, and apoptosis. Although many of these sirtuins have not been directly implicated in ischemic protection, they may have unique roles in enhancing function and preventing against stress-mediated cellular damage and death. This review will include in-depth analyses of the roles of CR, resveratrol, and IPC in activating sirtuins and in mediating protection against ischemic damage in the heart and brain.
authors.affiliation: Department of Neurology, Cerebral Vascular Disease Research Center, University of Miami, Miller School of Medicine, Miami, Florida 33101, USA.
authors.forename: Kahlilia C
authors.initials: KC
authors.lastname: Morris
authors.forename: Hung Wen
authors.initials: HW
authors.lastname: Lin
authors.forename: John W
authors.initials: JW
authors.lastname: Thompson
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Perez-Pinzon
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001711:Biotransformation; D002545:Brain Ischemia / Q000473:pathology; D031204:Caloric Restriction; D016923:Cell Death / Q000187:drug effects; D004249:DNA Damage; D006801:Humans; D019194:Ischemic Preconditioning; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D000077185:Resveratrol; D015398:Signal Transduction / Q000502:physiology; D056564:Sirtuin 1 / Q000235:genetics / Q000502:physiology; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; C510661:SIRT7 protein, human; D013267:Stilbenes; C447939:SIRT1 protein, human; C516592:SIRT6 protein, human; D056564:Sirtuin 1; D037761:Sirtuins; D000077185:Resveratrol