title: Diabetes-Induced Oxidative Stress in Endothelial Progenitor Cells May Be Sustained by a Positive Feedback Loop Involving High Mobility Group Box-1.
abstract: Oxidative stress is considered to be a critical factor in diabetes-induced endothelial progenitor cell (EPC) dysfunction, although the underlying mechanisms are not fully understood. In this study, we investigated the role of high mobility group box-1 (HMGB-1) in diabetes-induced oxidative stress. HMGB-1 was upregulated in both serum and bone marrow-derived monocytes from diabetic mice compared with control mice. In vitro, advanced glycation end productions (AGEs) induced, expression of HMGB-1 in EPCs and in cell culture supernatants in a dose-dependent manner. However, inhibition of oxidative stress with N-acetylcysteine (NAC) partially inhibited the induction of HMGB-1 induced by AGEs. Furthermore, p66shc expression in EPCs induced by AGEs was abrogated by incubation with glycyrrhizin (Gly), while increased superoxide dismutase (SOD) activity in cell culture supernatants was observed in the Gly treated group. Thus, HMGB-1 may play an important role in diabetes-induced oxidative stress in EPCs via a positive feedback loop involving the AGE/reactive oxygen species/HMGB-1 pathway.
authors.affiliation: Department of Cardiology, Drown Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
authors.forename: Han
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Cardiology, Drown Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Cardiology, Drown Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
authors.forename: Zhong-Hai
authors.initials: ZH
authors.lastname: Wei
authors.affiliation: Department of Cardiology, Drown Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
authors.forename: Xin-Lin
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Drown Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
authors.forename: Jian-Zhou
authors.initials: JZ
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Drown Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Dai
authors.affiliation: Department of Cardiology, Drown Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Cardiology, Drown Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Xu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D066026:Endothelial Progenitor Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D025461:Feedback, Physiological; D017127:Glycation End Products, Advanced / Q000378:metabolism; D019695:Glycyrrhizic Acid / Q000494:pharmacology; D024243:HMGB1 Protein / Q000097:blood / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009000:Monocytes / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D055765:Shc Signaling Adaptor Proteins / Q000378:metabolism; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D019695:Glycyrrhizic Acid; D000111:Acetylcysteine