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Involvement of cyclin‐dependent kinases in axotomy‐induced retinal ganglion cell death
Author(s) -
Lefèvre Karine,
Clarke Peter G.H.,
Danthe Eve E.,
Castagné Vincent
Publication year - 2002
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.10215
Subject(s) - axotomy , biology , cyclin dependent kinase , cyclin dependent kinase 1 , cyclin dependent kinase 5 , microbiology and biotechnology , cell cycle , spiral ganglion , cyclin dependent kinase 2 , kinase , neuroscience , apoptosis , protein kinase a , biochemistry , regeneration (biology) , inner ear
We have tested the role of cyclin‐dependent kinases (CDKs) in the type 3B death of axotomized retinal ganglion cells, by injecting intraocularly olomoucine, roscovitine, or butyrolactone I. Each of these inhibits CDK1, CDK2, and CDK5; CDK1 and CDK2 are involved in cell proliferation, whereas CDK5 is involved in neuronal differentiation. The inhibitors partially protected ganglion cells against the effects of axotomy. These agents may affect the ganglion cells directly, because CDK1, its regulatory subunit cyclin B1, and CDK5 were identified immunohistochemically in the perikarya of ganglion cells, and this was confirmed for CDK1 and CDK5 in Western blots of the ganglion cell layer. These blots showed an axotomy‐induced phosphorylation of CDK5 occurring remarkably quickly (within 6 hours of axotomy) but little if any change in the phosphorylation state of CDK1. In addition, we studied the expression of proliferation markers, including proliferating cell nuclear antigen (PCNA) and the synthesis of DNA, by immunohistochemical and autoradiographic methods. Normal or axotomized ganglion cells did not express PCNA and did not synthesize DNA. Although we cannot exclude the possibility that axotomized ganglion cells may leave their quiescent state, our data show that they did not progress beyond the G1 phase of the cell cycle. Finally, in contrast to inhibitors of CDKs, cell cycle blockers with different targets than CDKs did not protect ganglion cells. Globally, our results suggest that axotomy‐induced death of ganglion cells involves the activation of CDK1, CDK2, or CDK5 (most probably CDK5) but not the full cell cycle machinery. J. Comp. Neurol. 447:72–81, 2002. © 2002 Wiley‐Liss, Inc.