Increased and type II-specific expression of peptidylarginine deiminase in activated microglia but not hyperplastic astrocytes following kainic acid-evoked neurodegeneration in the rat brain

Abstract

Peptidylarginine deiminases (PADs) are a group of posttranslational modification enzymes that convert protein arginine residues to citrulline residues. In the rat cerebrum, the type II PAD is thought to be expressed mainly in glial cells, especially astrocytes, and to become activated early in the neurodegenerative process. To determine whether hyperplastic glial cells express PAD type II, we examined the rat brain after kainic acid-evoked neurodegeneration. Western blot and reverse transcriptase-polymerase chain reaction analyses revealed increased and type II-specific expression of PAD in the brain at 4-7 days after kainate administration. Immunocytochemically, no PAD type II immunoreactivity was observed in the glial fibrillary acidic protein-positive astrocytes, but such immunoreactivity was present coincident with a microglial marker recognized by Bandeiraea simplicifolia isolectin B4 in the damaged regions. These results clearly indicate that PAD type II is specifically and abundantly expressed in activated microglial cells and suppressed in hyperplastic astrocytes following neurodegeneration.