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

Authors


A. Kurtz, Institut für Physiologie, Universität Regensburg, D-93040 Regensburg, Germany. Fax: + 49 941 943 4315, Tel.: + 49 941 943 2980, E-mail: armin.kurtz@vkl.uni-regensburg.de

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 α but not of the isoform ERO1-Lβ are stimulated by hypoxia in rats vivo and in rat, mouse and human cell cultures. The temporal pattern of hypoxic ERO1-Lα 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-1β). We speculate from these findings that the expression of ERO1-Lα 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-Lβ and more moderately ERO1-Lα expression. The expression of the two ERO1-L isoforms therefore appears to be differently regulated, in the way that ERO1-Lα expression is mainly controlled by the cellular oxygen tension, whilst ERO1-Lβ is triggered mainly by UPR. The physiological meaning of the oxygen regulation of ERO1-Lα 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.

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