The endoplasmic reticulum is the main site for caspase-3 activation following aluminum-induced neurotoxicity in rabbit hippocampus

• Published in: Neuroscience letters Vol. 324; no. 3; pp. 217 - 221
• Main Authors: GHRIBI, Othman, HERMAN, Mary M, SAVORY, John
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier 24-05-2002
• Subjects: Animals; Apoptosis - drug effects; Apoptosis - physiology; Biological and medical sciences; Calcium-Binding Proteins - metabolism; Calnexin; Caspase 3; Caspases - metabolism; Chemical and industrial products toxicology. Toxic occupational diseases; Disease Models, Animal; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - enzymology; Endoplasmic Reticulum - ultrastructure; Female; Hippocampus - drug effects; Hippocampus - enzymology; Hippocampus - ultrastructure; Immunohistochemistry; Medical sciences; Metals and various inorganic compounds; Microscopy, Electron; Neurodegenerative Diseases - enzymology; Neurodegenerative Diseases - pathology; Neurodegenerative Diseases - physiopathology; Neurons - drug effects; Neurons - enzymology; Neurons - ultrastructure; Neurotoxins - toxicity; Organometallic Compounds - toxicity; Pyrones - toxicity; Rabbits; Toxicology; Enzyme; Toxicity; Central nervous system; Caspase; Rabbit; Aluminium; Lagomorpha; Peptidases; Vertebrata; Mammalia; Animal; Hydrolases; Endoplasmic reticulum; Hippocampus; Brain (vertebrata); Apoptosis
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(02)00147-7

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.