Hyperactivity of the Ero1α Oxidase Elicits Endoplasmic Reticulum Stress but No Broad Antioxidant Response

摘要: Oxidizing equivalents for the process of oxidative protein folding in endoplasmic reticulum (ER) mammalian cells are mainly provided by Ero1α oxidase. The molecular mechanisms that regulate activity order to harness its power quite well understood. However, overall cellular response stress generated lumen ER is poorly characterized. Here we investigate effects overexpressing a hyperactive mutant (C104A/C131A) Ero1α. We show hyperactivity leads hyperoxidation oxidoreductase ERp57 and induces expression two established unfolded (UPR) targets, BiP (immunoglobulin-binding protein) HERP (homocysteine-induced protein). These could be reverted or aggravated N-acetylcysteine buthionine sulfoximine, respectively. Because both agents manipulate glutathione redox buffer, conclude observed Ero1α-C104A/C131A overexpression likely caused an perturbation buffer. In accordance, affects cell viability when levels compromised. Using microarray analysis, demonstrate reacts challenge turning on UPR. Moreover, this analysis allowed identification new targets UPR, CRELD1 c18orf45. Interestingly, broad antioxidant was not induced. Our findings suggest addressed unlikely exert injury throughout cell.