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


OBJECTIVE
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).
Zocche Soprana
Hélen
H
Department of Clinical Analysis, Center of Health Sciences, Federal University of Santa Catarina, Brazil.
Canes Souza
Liliete
L
Debbas
Victor
V
Martins Laurindo
Francisco Rafael
FR
D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000293:injuries / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D003300:Copper / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction; D007083:Iliac Artery / Q000201:enzymology / Q000293:injuries / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000293:injuries / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D018621:PrPC Proteins / Q000096:biosynthesis*; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000096:biosynthesis*
D018621:PrPC Proteins; D003300:Copper; D013482:Superoxide Dismutase