ER stress inducer, thapsigargin, decreases extracellular-superoxide dismutase through MEK/ERK signalling cascades in COS7 cells

Author： Kamiya Tetsuro Obara Aya Hara Hirokazu Inagaki Naoki Adachi Tetsuo

Publisher： Informa Healthcare

ISSN： 1071-5762

Source： Free Radical Research, Vol.45, Iss.6, 2011-06, pp. : 692-698

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Abstract

AbstractIt has been reported that tubular cells suffer an endoplasmic reticulum (ER) stress during the development of chronic kidney disease, which is a potent risk factor of cardiovascular disease. Moreover, under these conditions, reactive oxygen species are generated and induce cell injury. Extracellular-superoxide dismutase (EC-SOD) is a member of SODs and protects the cells from oxidative stress. Here, it is demonstrated that thapsigargin, an ER stress inducer, decreased EC-SOD expression, whereas the expression of Cu,Zn-SOD and Mn-SOD was not changed. On the other hand, another ER stress inducer, tunicamycin, did not affect the expression of EC-SOD. Further, it was shown that thapsigargin has the ability to activate extracellular-signal regulated kinase (ERK), but tunicamycin does not. Moreover, pre-treatment with U0126, an inhibitor of mitogen-activated protein kinase kinase (MEK)/ERK, suppressed thapsigargin-triggered EC-SOD reduction, suggesting that MEK/ERK signalling should play an important role in the regulation of EC-SOD in COS7 cells under ER stress conditions.