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

• Published in: Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie 2011-03, Vol.63 (3), p.229-236
• Main Authors: Zocche Soprana, Hélen, Canes Souza, Liliete, Debbas, Victor, Martins Laurindo, Francisco Rafael
• Format: Article
• Language: English
• Subjects: Angiotensin II; Animals; antioxidant activity; Antioxidants; Aorta; Aorta - enzymology; Aorta - injuries; Aorta - metabolism; Arteries; Balloons; Biological and medical sciences; Blotting, Western; Catheters; Cell Line; Cellular prion protein; Copper; Copper - metabolism; Copper concentration; cytochrome c; Electrophoresis, Polyacrylamide Gel; Endoplasmic reticulum; Endoplasmic reticulum stress; enzyme activity; Enzyme Induction; exposure duration; Gene expression; Iliac Artery - enzymology; Iliac Artery - injuries; Iliac Artery - metabolism; in vivo studies; Injuries; Investigative techniques, diagnostic techniques (general aspects); Isoenzymes; isozymes; Male; Medical sciences; messenger RNA; Metabolism; Muscle, Smooth, Vascular - enzymology; Muscle, Smooth, Vascular - injuries; Muscle, Smooth, Vascular - metabolism; myocytes; Oxidative stress; Oxidative Stress - drug effects; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Polymerase chain reaction; Prion protein; prions; PrPC Proteins - biosynthesis; Rabbit aortic smooth muscle cells; Rabbits; Reverse Transcriptase Polymerase Chain Reaction; Smooth muscle; Superoxide dismutase; Superoxide Dismutase - biosynthesis; Tunicamycin; Western blotting
• ISSN: 0940-2993; 1618-1433
• DOI: 10.1016/j.etp.2009.12.004

The PrP C is expressed in several cell types but its physiological function is unknown. Some studies associate the PrP C with copper metabolism and the antioxidant activity of SOD. Our hypothesis was that changes in PrP C expression lead to abnormal copper regulation and induce SOD downregulation in the vascular wall. Objectives: to study whether the PrP C 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. PrP C expression decreased after exposure to all agents after different incubation periods. RT-PCR assay showed increased mRNA expression for PrP C only in cells stimulated for 8 hours with the different stressors. The PrP C mRNA expression in rabbit aortic artery fragments, subjected to balloon catheter injury, showed a pronounced increase immediately after overdistension. The results obtained indicated a PrP C protection factor during the early part of the ERS exposure period, but did not demonstrate a SOD-like profile for the PrP C.