title: Protection effect of nicotinamide on cardiomyoblast hypoxia/re-oxygenation injury: study of cellular mitochondrial metabolism.
abstract: Hypoxia/re-oxygenation (H/R) injury is an important cause of heart failure and results in a critical metabolism dysfunction. In this paper, the cytoprotective effect of the nicotinamide adenine dinucleotide (NAD) precursor nicotinamide was evaluated using an in vitro model of cardiac H/R injury. Nicotinamide (0-20 mM) was applied to the myoblast cell line H9c2 which was subjected to hypoxia (12, 24, 36 h) followed by a re-oxygenation process (0, 4, 8, 12 h). Cell viability was measured, and mitochondrial metabolites were extracted and then measured by HPLC/MS/MS. The present study showed that nicotinamide could down-regulate the NADH/NAD ratio and then maintain the NAD-dependent metabolism processes. Furthermore, an aberrant decrease of fumarate levels and an increase of succinate levels were observed in the nicotinamide group, which was demonstrated to be caused by nicotinamide-induced succinate dehydrogenase (SDH) inhibition. These results suggest that nicotinamide exerts a protective effect on cardiomyoblasts against H/R-induced injury through both NADH/NAD regulation and reduction of reactive oxygen species generation via SDH inhibition.
authors.affiliation: Beijing Key Lab of Microanalytical Methods & Instrumentation, Key lab of Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. China. liangql@mail.tsinghua.edu.cn liangxp@mail.tsinghua.edu.cn.
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.affiliation: Beijing Key Lab of Microanalytical Methods & Instrumentation, Key lab of Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. China. liangql@mail.tsinghua.edu.cn liangxp@mail.tsinghua.edu.cn.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liang
authors.affiliation: Beijing Key Lab of Microanalytical Methods & Instrumentation, Key lab of Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. China. liangql@mail.tsinghua.edu.cn liangxp@mail.tsinghua.edu.cn.
authors.forename: Guoan
authors.initials: G
authors.lastname: Luo
authors.affiliation: Beijing Key Lab of Microanalytical Methods & Instrumentation, Key lab of Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. China. liangql@mail.tsinghua.edu.cn liangxp@mail.tsinghua.edu.cn.
authors.forename: Mingyu
authors.initials: M
authors.lastname: Ding
authors.affiliation: Beijing Key Lab of Microanalytical Methods & Instrumentation, Key lab of Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. China. liangql@mail.tsinghua.edu.cn liangxp@mail.tsinghua.edu.cn.
authors.forename: Qionglin
authors.initials: Q
authors.lastname: Liang
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002952:Citric Acid Cycle / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000860:Hypoxia; D055432:Metabolomics / Q000379:methods; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D032386:Myoblasts, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*; D009536:Niacinamide / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species
chemical_list: D020011:Protective Agents; D017382:Reactive Oxygen Species; D009536:Niacinamide