title: A HIF-1alpha-related gene involved in cell protection from hypoxia by suppression of mitochondrial function.
abstract: Recently, we reported that acetylcholine-induced hypoxia-inducible factor-1alpha protects cardiomyocytes from hypoxia; however, the downstream factors reducing hypoxic stress are unknown. We identified apoptosis inhibitor (AI) gene as being differentially expressed between von Hippel Lindau (VHL) protein-positive cells with high levels of GRP78 expression and VHL-negative cells with lower GRP levels, using cDNA subtraction. AI decreased GRP78 level, suppressed mitochondrial function, reduced oxygen consumption and, ultimately, suppressed hypoxia-induced apoptosis. By contrast, knockdown of the AI gene increased mitochondrial function. Hypoxic cardiomyocytes and ischemic myocardium showed increased AI mRNA expression. These findings suggest that AI is involved in suppressing mitochondrial function, thereby leading to cellular stress eradication and consequently to protection during hypoxia.
authors.affiliation: Department of Cardiovascular Control, Kochi Medical School, Nankoku, Japan. kakinuma@kochi-u.ac.jp
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kakinuma
authors.forename: Rajesh G
authors.initials: RG
authors.lastname: Katare
authors.forename: Mikihiko
authors.initials: M
authors.lastname: Arikawa
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Muramoto
authors.forename: Fumiyasu
authors.initials: F
authors.lastname: Yamasaki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sato
mesh_terms: D000818:Animals; D001483:Base Sequence; D015687:Cell Hypoxia / Q000235:genetics*; D002460:Cell Line; D017931:DNA Primers; D018076:DNA, Complementary; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D008928:Mitochondria / Q000502:physiology*; D018832:Molecular Chaperones / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D000091342:Endoplasmic Reticulum Chaperone BiP; C497442:HIF1A protein, human; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051034:Inhibitor of Apoptosis Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human