title: AGEs Decreased SIRT3 Expression and SIRT3 Activation Protected AGEs-Induced EPCs' Dysfunction and Strengthened Anti-oxidant Capacity.
abstract: Advanced glycation end products (AGEs) have been confirmed to induce dysfunction in endothelial progenitor cells (EPCs) and play key roles in pathogenesis of diabetes-related vascular complications. The major function of sirtuin 3 (SIRT3) is to orchestrate oxidative metabolism and control reactive oxygen species (ROS) homeostasis, which are more closely related to EPCs' dysfunction. Our study therefore was designed to explore the role of SIRT3 on AGEs-induced EPCs dysfunction of. EPCs isolated from healthy adults were stimulated with AGEs and the expression of SIRT3 was assessed. Then, EPCs transfected with ad-SIRT3 or siRNA-SIRT3 were cultured with or without AGEs. EPCs function, including proliferation, migration; expression of manganese superoxide dismutase (MnSOD), ROS production, and interleukin-8 (IL-8); and vascular endothelial growth factor (VEGF) production were measured. In some experiments, EPCs were pre-cultured with anti-receptor for advanced glycation end products (RAGE) antibody or anti-neutralizing antibody, and then proliferation, migration, expression of MnSOD, ROS production, and IL-8 and VEGF production were measured. Our results showed that SIRT3 expressed in EPCs and AGEs decreased SIRT3 expression. SIRT3 knockdown with siRNA-SIRT3 promoted dysfunction in EPCs whereas SIRT3 activation with ad-SIRT3 strengthened anti-oxidant capacity and protected AGE-impaired dysfunction. Moreover, RAGE may involve in AGEs-decreased SIRT3 expression in EPCs. These data suggested an important role of SIRT3 in regulating EPCs bioactivity.
authors.affiliation: Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Disease of Education Ministry, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.|Department of Neurology, Xi'an Central Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
authors.forename: Mingze
authors.initials: M
authors.lastname: Chang
authors.affiliation: Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Disease of Education Ministry, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Disease of Education Ministry, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Disease of Education Ministry, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Neurology, Xi'an Central Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
authors.forename: Gejuan
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Xi'an Central Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
authors.forename: Zhengli
authors.initials: Z
authors.lastname: Di
authors.affiliation: Department of Neurology, Xi'an Central Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
authors.forename: Xinlai
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Disease of Education Ministry, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Disease of Education Ministry, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
authors.forename: Naibin
authors.initials: N
authors.lastname: Gu
authors.affiliation: Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Disease of Education Ministry, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China. xiuyu654@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D066026:Endothelial Progenitor Cells / Q000187:drug effects / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000494:pharmacology; D006801:Humans; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D056566:Sirtuin 3 / Q000187:drug effects / Q000378:metabolism*
chemical_list: C000593871:AGER protein, human; D000975:Antioxidants; D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D056566:Sirtuin 3
keywords: AGEs; MnSOD; RAGE; ROS; SIRT3; endothelial progenitor cells