Increased peptidylarginine deiminase type II in hypoxic astrocytes.
Peptidylarginine deiminase type II (PAD 2) is the primary enzyme responsible for conversion of protein bound arginine to citrulline in the central nervous system. Evidence suggests that glial fibrillary acidic protein (GFAP), the main intermediate filament in astrocytes, is deiminated, but not much is known regarding factors that control this enzymatic reaction. The present study demonstrated that PAD 2 activity (as determined by Western blot analysis of citrullinated GFAP isoforms) was increased in human cultured astrocytes by hypoxic conditions. PAD 2 mRNA increased markedly during the first 2h of hypoxia, but using a single chain antibody against human PAD 2 produced from the ETH-2 phage library, it took approximately 8h of hypoxia to see marked increases in PAD 2 protein. Thus, this is the first report to demonstrate a measurable response in the amounts of PAD 2 mRNA, protein and activity in human astrocytes by prolonged hypoxic exposure.
Sambandam
Thiagarajan
T
Department of Neurology, University of Alabama at Birmingham, School of Medicine, Birmingham, AL 35294, USA.
Belousova
Maria
M
Accaviti-Loper
Mary Ann
MA
Blanquicett
Carmelo
C
Guercello
Vincenzo
V
Raijmakers
Reinout
R
Nicholas
Anthony P
AP
D000222:Adaptation, Physiological / Q000502:physiology; D001253:Astrocytes / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D004789:Enzyme Activation; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D006801:Humans; D006867:Hydrolases / Q000145:classification / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D000076342:Protein-Arginine Deiminases
D005904:Glial Fibrillary Acidic Protein; D006867:Hydrolases; D000076342:Protein-Arginine Deiminases; D010100:Oxygen