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Kainate‐Induced Apoptosis in Cultured Murine Cerebellar Granule Cells Elevates Expression of the Cell Cycle Gene Cyclin D1
Author(s) -
Giardina Sarah F.,
Cheung Nam S.,
Reid Michelle T.,
Beart Philip M.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.71031325.x
Subject(s) - biology , cyclin d1 , cell cycle , kainate receptor , apoptosis , microbiology and biotechnology , cyclin a , glutamate receptor , receptor , biochemistry , ampa receptor
Recent evidence suggests that neuronal apoptosis is the consequence of an inappropriate reentry into the cell cycle. Expression of the cell cycle gene cyclin D1, a G1‐phase cell cycle regulator, was examined in primary cultures of murine cerebellar granule cells (CGCs) during kainate (KA)‐mediated apoptosis. Using cultures of CGCs, we found that a 24‐h exposure to KA (1–3,000 µ M ) induced a concentration‐dependent cell death with neurons exhibiting characteristic apoptotic morphology and extensive labeling using the terminal transferase‐mediated nick end‐DNA labeling (TUNEL) method. KA induced a time‐ and concentration‐dependent increase in expression of cyclin D1 as determined by immunocytochemistry and western blot analysis. KA‐induced apoptosis and cyclin D1 expression exhibited a similar concentration dependence and were significantly attenuated by the non‐NMDA receptor antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (50 µ M ), indicating a KA receptor‐mediated effect. Here we present evidence for the first time that KA‐induced apoptosis in cultured CGCs involves the induction of cyclin D1, suggesting its involvement in excitotoxic receptor‐mediated apoptosis.