Article

Increased peptidylarginine deiminase type II in hypoxic astrocytes.

Department of Neurology, University of Alabama at Birmingham, School of Medicine, Birmingham, AL 35294, USA.
Biochemical and Biophysical Research Communications (impact factor: 2.48). 01/2005; 325(4):1324-9. DOI:10.1016/j.bbrc.2004.10.173 pp.1324-9
Source: PubMed

ABSTRACT 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.

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Keywords

arginine
 
central nervous system
 
citrullinated GFAP isoforms
 
first 2h
 
first report
 
glial fibrillary acidic protein
 
human cultured astrocytes
 
human PAD 2
 
hypoxic conditions
 
hypoxic exposure
 
measurable response
 
PAD 2
 
PAD 2 activity
 
PAD 2 mRNA
 
PAD 2 protein
 
Peptidylarginine deiminase type II
 
primary enzyme responsible
 
single chain antibody
 
Western blot analysis