Protein deimination in the rat brain after kainate administration: citrulline-containing proteins as a novel marker of neurodegeneration.
Peptidylarginine deiminases (PADs) are a group of enzymes that convert protein arginine residues to citrulline residues in a Ca2+-dependent manner. In the central nervous system, PAD type II localizes in glial cells, but its biological role is little understood. We examined the timing and region dependence of protein deimination in the rat cerebrum after a systemic injection of kainic acid (KA). Citrulline-containing proteins were consistently found in neurodegenerating regions. Western blot analyses showed deimination of numerous proteins in a broad-molecular-weight range. By immunocytochemical scrutiny, deiminated protein-positive astrocytes were found at 2 h after KA administration, and they increased in number until the 6 h. Furthermore, shrunken neurons became deiminated protein-positive at 12-24 h. These data suggest that PAD type II becomes activated in regions undergoing neurodegeneration and functions to deiminate various proteins. Therefore, citrulline-containing proteins seem to be a useful marker of acute neurodegeneration.
Asaga
H
H
Department of Bioactivity Regulation, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan. sasgahi@tmig.or.jp
Ishigami
A
A
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002956:Citrulline / Q000378:metabolism*; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006867:Hydrolases / Q000378:metabolism*; D007097:Imines / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism*; D009457:Neuroglia / Q000201:enzymology / Q000473:pathology; D009474:Neurons / Q000473:pathology; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D051381:Rats; D017208:Rats, Wistar; D013687:Telencephalon / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology
D015415:Biomarkers; D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D007097:Imines; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D002956:Citrulline; D006867:Hydrolases; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D007608:Kainic Acid