The cellular oxygen tension regulates expression of the endoplasmic oxidoreductase ERO1-Lalpha.

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Gess B, Hofbauer KH, Wenger RH, Lohaus C, Meyer HE, Kurtz A

The cellular oxygen tension regulates expression of the endoplasmic oxidoreductase ERO1-Lalpha.

Eur J Biochem. 2003 May;270(10):2228-35.

PubMed ID

12752442 [ View in PubMed

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Abstract

The formation of disulfide bonds in the endoplasmic reticulum requires protein disulfide isomerase (PDI) and endoplasmic reticulum oxidoreductin 1 (ERO1) that reoxidizes PDI. We report here that the expression of the rat, mouse and human homologues of ERO1-Like protein alpha but not of the isoform ERO1-Lbeta are stimulated by hypoxia in rats vivo and in rat, mouse and human cell cultures. The temporal pattern of hypoxic ERO1-Lalpha induction is very similar to that of genes triggered by the hypoxia inducible transcription factor (HIF-1) and is characteristically mimicked by cobalt and by deferoxamine, but is absent in cells with a defective aryl hydrocarbon receptor translocator (ARNT, HIF-1beta). We speculate from these findings that the expression of ERO1-Lalpha is probably regulated via the HIF-pathway and thus belongs to the family of classic oxygen regulated genes. Activation of the unfolded protein response (UPR) by tunicamycin, on the other hand, strongly induced ERO1-Lbeta and more moderately ERO1-Lalpha expression. The expression of the two ERO1-L isoforms therefore appears to be differently regulated, in the way that ERO1-Lalpha expression is mainly controlled by the cellular oxygen tension, whilst ERO1-Lbeta is triggered mainly by UPR. The physiological meaning of the oxygen regulation of ERO1-Lalpha expression likely is to maintain the transfer rate of oxidizing equivalents to PDI in situations of an altered cellular redox state induced by changes of the cellular oxygen tension.

DrugBank Data that Cites this Article

Polypeptides

Name	UniProt ID
ERO1-like protein beta	Q86YB8	Details

Pharmaco-transcriptomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Deferoxamine	Approved Investigational	ERO1A	30001	upregulated	Deferoxamine results in increased expression of ERO1A mRNA	14q22.1