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Differentiation‐dependent sensitivity to cell death induced in the developing retina by inhibitors of the ubiquitin‐proteasome proteolytic pathway
Author(s) -
Neves D. D. C.,
Rehen S. K.,
Linden R.
Publication year - 2001
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.0953-816x.2001.01571.x
Subject(s) - mg132 , microbiology and biotechnology , proteasome inhibitor , biology , proteasome , programmed cell death , cell cycle , anisomycin , apoptosis , retina , population , neuroscience , biochemistry , medicine , environmental health , kinase
The effects of inhibitors of proteasome function were studied in the retina of developing rats. Explants from the retina of neonatal rats at postnatal day (P) 3 or P6 were incubated with various combinations of the proteasome inhibitor carbobenzoxyl‐leucinyl‐leucinyl‐leucinal (MG132), the protein synthesis inhibitor anisomycin, or the adenylyl cyclase activator forskolin. MG132 induced cell death in a subset of cells within the neuroblastic (proliferative) layer of the retinal tissue. The cells sensitive to degeneration induced by either MG132 or anisomycin, were birthdated by bromodeoxyuridine injections. This showed that the MG132‐sensitive population includes both proliferating cells most likely in their last round of cell division, and postmitotic undifferentiated cells, at a slightly earlier stage than the population, sensitive to anisomycin‐induced cell death. The results show that sensitivity to cell death induced by proteasome inhibitors defines a window of development in the transition from the cell cycle to the differentiated state in retinal cells.