title: Apelin-APJ effects of ginsenoside-Rb1 depending on hypoxia-induced factor 1α in hypoxia neonatal cardiomyocytes.
abstract: OBJECTIVE
  To investigate whether ginsenoside-Rb1 (Gs-Rb1) inhibits the apoptosis of hypoxia cardiomyocytes by up-regulating apelin-APJ system and whether the system is affected by hypoxia-induced factor 1α (Hif-1α).
  
  
  METHODS
  Neonatal rat cardiomyocytes were randomly divided into 6 groups: a control group, a simple CoCl group, a simple Gs-Rb1 group, a CoCl and Gs-Rb1 hypoxia group, a CoCl and 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) group, a CoCl and YC-1 group and a Gs-Rb1 group, in which YC-1 inhibits the synthesis and accelerates the degradation of Hif-1a. The concentration of CoCl, Gs-Rb1 and YC-1 was 500 μmol/L, 200 μmol/L and 5 μmol/L, respectively; the apoptosis ratio was analyzed with a flow cytometer; and apelin, APJ and Hif-1α were assayed with immunocytochemistry, Western blot assays and reverse transcription polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  (1) The anti-apoptosis effect of Gs-Rb1 on hypoxia cardiomyocytes was significantly inhibited by YC-1; (2) Hypoxia significantly up-graded the expression of mRNA and protein of apelin; this effect was further reinforced by Gs-Rb1 and significantly inhibited by YC-1; (3) Gs-Rb1 further strengthened the expression of APJ mRNA and APJ proteins once hypoxia occurred, which was significantly inhibited by YC-1; (4) Gs-Rb1 significantly increased the expression of Hif-1α, which was completely abolished by YC-1; (5) There was a negative relationship between AR and apelin (or APJ, including mRNA and protein), a positive correlation between apelin (or APJ) protein and Hif-1a protein, in hypoxia cardiomyocytes.
  
  
  CONCLUSIONS
  The apelin-APJ system plays an important role in the anti-apoptosis effect of Gs-Rb1 on hypoxia neonatal cardiomyocytes, which was partly adjusted by Hif-1α.
authors.affiliation: Cardiology Center, The People's Hospital of Liaoning Province, Shenyang, 110016, China, kh1339@sina.com.
authors.forename: Hong-liang
authors.initials: HL
authors.lastname: Kong
authors.forename: Zhan-quan
authors.initials: ZQ
authors.lastname: Li
authors.forename: Shu-mei
authors.initials: SM
authors.lastname: Zhao
authors.forename: Long
authors.initials: L
authors.lastname: Yuan
authors.forename: Zhi-lin
authors.initials: ZL
authors.lastname: Miao
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Ru-ming
authors.initials: RM
authors.lastname: Guan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000073861:Apelin; D000075244:Apelin Receptors; D015687:Cell Hypoxia / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: D000073861:Apelin; D000075244:Apelin Receptors; C498579:Apln protein, rat; C491284:Aplnr protein, rat; D036145:Ginsenosides; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C442759:ginsenoside Rb1