A possible role for PKC delta in cerebellar granule cells apoptosis.
Cerebellar granule cells (CGC) undergo massive DNA fragmentation, an apoptotic marker, in 8-day-old rat cerebellum. In vitro, they survive in the presence of depolarizing concentrations of KCl. Bisindolylmaleimide, a specific PKC inhibitor, blocks CGC apoptosis in vitro. Here I show that PKC delta, which has been involved in apoptosis in different cell lines, is constitutively cleaved in CGC, suggesting that its catalytic subunit is active per se. Moreover, KCl deprivation induces cyclin D1 expression and accumulation in nuclei. This process is blocked by bisindolylmaleimide. A model is proposed where, in the absence of survival signals, activated PKC delta induces cyclin D1 expression and accumulation in the nucleus, which subsequently, would lead to an aborted cell cycle and apoptosis.
CNRS UPR-9023, Mecanismes Moleculaires des Communications Cellulaires, CCIPE, Montpellier, France.
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M
Villalba
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D019938:Cyclin D1 / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008301:Maleimides / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051745:Protein Kinase C-delta; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D007211:Indoles; D007527:Isoenzymes; D008301:Maleimides; D019938:Cyclin D1; D011189:Potassium Chloride; C497260:Prkcd protein, rat; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; C088060:bisindolylmaleimide