Open AccessOxygen tension regulates the expression of a group of procollagen hydroxylases
Author(s) -
Hofbauer KarlHeinz,
Gess Bernhard,
Lohaus Christiane,
Meyer Helmut E.,
Katschinski Dörte,
Kurtz Armin
Publication year - 2003
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1033.2003.03846.x
Subject(s) - hypoxia (environmental) , procollagen peptidase , cell culture , biology , gene expression , microbiology and biotechnology , oxygen tension , embryonic stem cell , cell , gene , transcription (linguistics) , hypoxia inducible factors , chemistry , biochemistry , oxygen , genetics , linguistics , philosophy , organic chemistry
In this study, we have characterized the influence of hypoxia on the expression of hydroxylases crucially involved in collagen fiber formation, such as prolyl‐4‐hydroxylases (Ph4) and procollagen lysyl‐hydroxylases (PLOD). Using the rat vascular smooth muscle cell line A7r5, we found that an hypoxic atmosphere caused a characteristic time‐dependent five‐ to 12‐fold up‐regulation of the mRNAs of the two P4h α‐subunits [αI (P4ha1) and αII (P4ha2)] and of two lysylhydroxylases (PLOD1 and PLOD2). These effects of hypoxia were mimicked by the iron‐chelator deferoxamine (100 µ m ) and by cobaltous chloride (100 µ m ). The hypoxic induction of these genes was also seen in the mouse juxtaglomerular As4.1 cell line and mouse hepatoma cell line Hepa1 but was almost absent in the mutant cell line Hepa1C4, which is defective for the hypoxia‐inducible transcription factor 1 (HIF‐1). In addition, the enzyme expression was induced by hypoxia in mouse embryonic fibroblasts but not in embryonic fibroblasts lacking the HIF‐1α subunit. These findings indicate that hypoxia stimulates the gene expression of a cluster of hydroxylases that are indispensible for collagen fiber formation. Strong indirect evidence, moreover, suggests that the expression of these enzymes during hypoxia is coordinated by HIF‐1.