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- Title
Differential Subcellular Redistribution of Protein Kinase C Isozymes in the Rat Hippocampus Induced by Kainic Acid.
- Authors
McNamara, Robert K.; Wees, Elizabeth A.; Lenox, Robert H.
- Abstract
Abstract: Protein kinase C (PKC) consists of a family of Ca2+/phospholipid-dependent isozymes that has been implicated in the delayed neurotoxic effects of glutamate in vitro. In the present study, we assessed the effect of the glutamate analogue kainic acid (KA) on the subcellular expression of PKC isozymes in the hippocampus (HPC) in the period preceding (0.5, 1.5, 12, and 24 h) and during (120 h) hippocampal necrosis using western blot analysis and PKC isozyme-specific antibodies. Before subcellular fractionation (cytosol + membrane), hippocampi were microdissected into “HPC” (fields CA1-CA3) and “dentate gyrus” (DG; granule cells + hilus) regions. Four general patterns of alterations in PKC isozyme expression/distribution were observed following KA treatment. The first pattern was a relative stability in expression following KA treatment and was most apparent for cytosol PKCα (HPC + DG) and membrane (HPC) and cytosol (DG) PKCβII. The second pattern, observed with PKCγ and PKCε, was characterized by an initial increase in expression in both membrane and cytosolic fractions before seizure activity (0.5 h) followed by a gradual decrease until significant reductions are observed by 120 h. The third pattern, exhibited by PKCδ, involved an apparent translocation, increasing in the membrane and decreasing in the cytosol, followed by down-regulation in both fractions and subsequent recovery. The fourth pattern was observed with PKCζ only and entailed a significant reduction in expression before and during limbic motor seizures followed by a dramatic fivefold increase in the membrane fraction during the period of hippocampal necrosis (120 h). Although these patterns did not segregate according to conventional PKC isozyme classifications, they do indicate dynamic isozyme-specific regulation by KA. The subcellular redistribution of PKC isozymes may contribute to the histopathological sequelae produced by KA in the hippocampus and may model the pathogenesis associated with diseases involving glutamate-induced neurotoxicity.
- Subjects
PROTEIN kinase C; HIPPOCAMPUS (Brain); KAINIC acid
- Publication
Journal of Neurochemistry, 1999, Vol 72, Issue 4, p1735
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1046/j.1471-4159.1999.721735.x