Retracted: The endoplasmic reticulum is the main site for caspase-3 activation following aluminum-induced neurotoxicity in rabbit hippocampus.
We have assessed the distribution of caspase-3 in subcellular fractions from rabbit brain hippocampus and find that in controls the pro-caspase-3 form is distributed mainly in the cytoplasm. In animals treated intracisternally with the neurotoxin aluminum-maltolate, although pro-caspase-3 levels are higher in the cytosolic fractions, p17, the active caspase-3, is localized mainly in the endoplasmic reticulum. This distribution is confirmed by immunohistochemistry which demonstrates the co-localization of p17 with calnexin, a specific marker of the endoplasmic reticulum. Based on the apparent translocation into the endoplasmic reticulum of active caspase-3, an executioner of cell death, the results suggest that this organelle is an important site in the caspase-3 mediated apoptosis cascade. Inhibition of the latter enzyme by directly targeting its main site of activation could represent a strategy to prevent this adverse event.
Ghribi
Othman
O
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
Herman
Mary M
MM
Savory
John
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D037281:Calnexin; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D019636:Neurodegenerative Diseases / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D009498:Neurotoxins / Q000633:toxicity; D009942:Organometallic Compounds / Q000633:toxicity; D011753:Pyrones / Q000633:toxicity; D011817:Rabbits
D002135:Calcium-Binding Proteins; D009498:Neurotoxins; D009942:Organometallic Compounds; D011753:Pyrones; D037281:Calnexin; C067527:aluminum maltolate; D053148:Caspase 3; D020169:Caspases