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A HIF‐1alpha‐related gene involved in cell protection from hypoxia by suppression of mitochondrial function
Author(s) -
Kakinuma Yoshihiko,
Katare Rajesh G.,
Arikawa Mikihiko,
Muramoto Kazuyo,
Yamasaki Fumiyasu,
Sato Takayuki
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.12.026
Subject(s) - hypoxia (environmental) , gene knockdown , apoptosis , mitochondrion , microbiology and biotechnology , biology , gene , gene expression , chemistry , oxygen , biochemistry , organic chemistry
Recently, we reported that acetylcholine‐induced hypoxia‐inducible factor‐1α 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.