Cellular prion protein (PrPC) and superoxide dismutase (SOD) in vascular cells under oxidative stress

The PrPC is expressed in several cell types but its physiological function is unknown. Some studies associate the PrPC with copper metabolism and the antioxidant activity of SOD. Our hypothesis was that changes in PrPC expression lead to abnormal copper regulation and induce SOD downregulation in the vascular wall. Objectives: to study whether the PrPC expression undergoes induction by agents that trigger endoplasmic reticulum stress (ERS) and, in this context, to evaluate the SOD activity. Methods: To trigger ERS, in vitro, rabbit aortic smooth muscle cells were challenged for 4, 8 and 18 hours, with angiotensin-II, tunicamycin and 7-ketocholesterol. For in vivo studies rabbit aortic arteries were subjected to injury by balloon catheter. Results: In vitro baseline SOD activity, determined through inhibition of cytochrome-c reduction, was 13.9 +/- 1.2 U/mg protein, angiotensin-II exposed for 8 hours produced an increase in SOD activity, and cellular copper concentration was about 9 times greater only under these conditions. Western blotting analysis for SOD isoenzymes showed an expression profile that was not correlated with the enzymatic activity. PrPC expression decreased after exposure to all agents after different incubation periods. RT-PCR assay showed increased mRNA expression for PrPC only in cells stimulated for 8 hours with the different stressors. The PrPC mRNA expression in rabbit aortic artery fragments, subjected to balloon catheter injury, showed a pronounced increase immediately after overdistension. The results obtained indicated a PrPC protection factor during the early part of the ERS exposure period, but did not demonstrate a SOD-like profile for the PrPC. (C) 2009 Elsevier GmbH. All rights reserved.