title: P66Shc-SIRT1 Regulation of Oxidative Stress Protects Against Cardio-cerebral Vascular Disease.
abstract: Growing evidence shows that acute and chronic overproduction of reactive oxygen species (ROS) and increased oxidants under pathophysiologic circumstances are of vital importance in the development of cardio-cerebral vascular diseases (CCVDs). It has been revealed that the impact of ROS can be suppressed by sirtuin 1 (SIRT1), a member of the highly conserved nicotinamide adenine dinucleotide-dependent class III histone deacetylases through protecting endothelial cells from oxidative injury. Plenty of evidences indicate that p66Shc stimulates mitochondrial ROS generation through its oxidoreductase activity and plays a vital role in the pathophysiology of CCVDs. The link between SIRT and p66Shc, though not very clear yet, may be generally illustrated like this: SIRT1 negatively regulates the expression of p66Shc in transcriptional level. In this review, the authors aimed to discuss the link between the pathogenesis of CCVDs, the regulation of ROS, the interrelation between SIRT1 and p66Shc, and the protective effect of the proper regulation of p66Shc/SIRT1 on CCVDs. The imbalance between the elimination and production of ROS can lead to oxidative stress (OS). More and more evidence suggest that ROS pathological overproduction is closely connected to the genesis and growth of CCVDs. P66shc is a gene that controls ROS level, apoptosis induction, and lifespan. Lots of evidence also indicate a role for SIRT1 mediating OS responses through several ways including directly deacetylating some transcription factors that control anti-OS genes. SIRT1 downregulation can lead to a decreased deacetylation of p66shc gene promoter and can then result in p66shc transcription. SIRT1 binds to the promoter of p66Shc where it can deacetylate histone H3, which weakens the transcription and translation of p66shc.
authors: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, People's Republic of China.|Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Harvard University, 55 Fruit Street, Boston, MA, 02114-3117, USA.
authors: Xiangyi
authors: X
authors: Kong
authors: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, People's Republic of China.
authors: Jian
authors: J
authors: Guan
authors: Department of Neurosurgery, Tangshan Gongren Hospital, Hebei Medical University, 27 Wenhua Road, Tangshan, 063000, People's Republic of China.
authors: Jun
authors: J
authors: Li
authors: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, People's Republic of China.
authors: Junji
authors: J
authors: Wei
authors: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, People's Republic of China. wangrenzhipumch@qq.com.
authors: Renzhi
authors: R
authors: Wang
mesh_terms: D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D056564:Sirtuin 1 / Q000378:metabolism*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1 / Q000378:metabolism*
chemical_list: D020011:Protective Agents; D017382:Reactive Oxygen Species; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D056564:Sirtuin 1
keywords: Cardio-cerebral vascular disease; Oxidative stress; P66Shc; Pathophysiological mechanism; SIRT1