Early nuclear exclusion of the transcription factor max is associated with retinal ganglion cell death independent of caspase activity.
We examined the behavior of the transcription factor Max during retrograde neuronal degeneration of retinal ganglion cells. Using immunohistochemistry, we found a progressive redistribution of full-length Max from the nucleus to the cytoplasm and dendrites of the ganglion cells following axon damage. Then, the axotomized cells lose all their content of Max, while undergoing nuclear pyknosis and apoptotic cell death. After treatment of retinal explants with either anisomycin or thapsigargin, the rate of nuclear exclusion of Max accompanied the rate of cell death as modulated by either drug. Treatment with a pan-caspase inhibitor abolished both TUNEL staining and immunoreactivity for activated caspase-3, but did not affect the subcellular redistribution of Max immunoreactivity after axotomy. The data show that nuclear exclusion of the transcription factor Max is an early event, which precedes and is independent of the activation of caspases, during apoptotic cell death in the central nervous system.
Petrs-Silva
Hilda
H
Instituto de Biofísica Carlos Chagas Filho, UFRJ, Rio de Janeiro, Brazil.
de Freitas
Fabíola G
FG
Linden
Rafael
R
Chiarini
Luciana B
LB
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D009410:Nerve Degeneration / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C499329:Max protein, rat; C067850:Myc associated factor X; D011500:Protein Synthesis Inhibitors; D014157:Transcription Factors; D019284:Thapsigargin; D000841:Anisomycin; D020169:Caspases