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 prot ein 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 dep endence of protein deimination in the rat cerebrum after a systemic injecti on of kainic acid (KA). Citrulline-containing proteins were consistently fo und in neurodegenerating regions. Western blot analyses showed deimination of numerous proteins in a broad-molecular-weight range. By immunocytochemic al 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 dat a suggest that PAD type II becomes activated in regions undergoing neurodeg eneration and functions to deiminate various proteins. Therefore, citrullin e-containing proteins seem to be a useful marker of acute neurodegeneration . (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.