title: Cross-talk between SIRT1 and p66Shc in vascular diseases.
abstract: Accumulating evidence indicates that oxidative stress can occur through overproduction of reactive oxygen species (ROS) and/or reduced anti-oxidant potentials under pathophysiological conditions and plays an important role in the development of cardiovascular diseases (CVDs). Adapter protein p66Shc has the property to directly stimulate mitochondrial ROS generation by an oxidoreductase activity. A growing body of evidence implies that p66Shc plays a critical role in the pathophysiology of age-related vascular diseases. Silent mating type information regulator 2 homolog 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylase (HDAC), has also been implicated in protection against vascular aging and age-related vascular diseases. Recently, we demonstrated that SIRT1 protects blood vessels from hyperglycemia-induced endothelial dysfunction through a novel mechanism involving the downregulation of p66Shc expression. In this review, we discuss the cross-talk between these two longevity genes as a mechanism of preventing vascular diseases by involving anti-oxidative stress responses and inhibiting endothelial senescence.
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, PR China.
authors.forename: Hou-Zao
authors.initials: HZ
authors.lastname: Chen
authors.forename: Yan-Zhen
authors.initials: YZ
authors.lastname: Wan
authors.forename: De-Pei
authors.initials: DP
authors.lastname: Liu
mesh_terms: D000818:Animals; D016922:Cellular Senescence / Q000235:genetics; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D008136:Longevity / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014652:Vascular Diseases / Q000235:genetics / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D056564:Sirtuin 1