title: Hypoxia-inducible factor 1α regulates the expression of the mitochondrial ATPase inhibitor protein (IF1) in rat liver.
abstract: A growing number of reports indicate that bioenergetic failure plays a crucial role in the development of multiple organ failure during sepsis. Our previous results showed that the suppression of IF1 (mitochondrial ATPase inhibitor protein) expression and subsequent elevated mitochondrial F(o)F₁-ATPase activity might contribute to the bioenergetic failure in the liver during sepsis, and the influence of the decreased transcriptional level of IF1 might be an important factor. In this study, we investigated the interaction of IF1 protein expression and hypoxia-inducible factor 1 (HIF-1), a transcription factor that is correlated with the inflammatory status in sepsis. The results showed that nuclear HIF-1α protein, a subunit of HIF-1, and IF1 mRNA expression were coincidently reduced in late septic liver of rats. Furthermore, in vitro, overexpression of HIF-1α by hypoxia or CoCl₂ (HIF-1α activator) treatment augmented IF1 protein levels. On the contrary, HIF-1α antisense oligonucleotide and siRNA were used to specifically downregulate HIF-1α expression, and then IF1 protein levels were significantly decreased in clone 9 cells. Meanwhile, downregulation of HIF-1α expression led to elevate the mitochondrial F(o)F₁-ATPase activity in the presence of Bis-Tris buffer (pH 6.5). In conclusion, these results suggested for the first time that the HIF-1 might play a crucial role in regulating IF1 protein expression in late septic liver.
authors.affiliation: Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Li-Ju
authors.initials: LJ
authors.lastname: Huang
authors.forename: I-Chun
authors.initials: IC
authors.lastname: Chuang
authors.forename: Huei-Ping
authors.initials: HP
authors.lastname: Dong
authors.forename: Rei-Cheng
authors.initials: RC
authors.lastname: Yang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000201:enzymology* / Q000378:metabolism*; D008297:Male; D024101:Mitochondrial Proteins; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000378:metabolism*; D000097795:ATPase Inhibitory Protein
chemical_list: D003035:Cobalt; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D024101:Mitochondrial Proteins; D016376:Oligonucleotides, Antisense; D011506:Proteins; D034741:RNA, Small Interfering; D000097795:ATPase Inhibitory Protein; C018021:cobaltous chloride