Effects of ICE-like protease and calpain inhibitors on neuronal apoptosis.
Both ice-like protease and calpain have been shown to be involved in apoptosis in non-neuronal cells. Cultured rat cerebellar granule neurons undergo apoptosis when exposed to low potassium-containing medium. Calpain inhibitors 3-(4-iodophenyl)-2-mercapto-(Z)-2-propenoic acid (PD150606) and N-acetyl-Leu-Leu-Met-CHO (calpain inhibitor II) as well as interleukin-beta 1 converting enzyme (ICE)-like protease inhibitor Z-Asp-CH2OC(O)-2,6-dichlorobenzene (Z-D-DCB) protect against such apoptotic death. They also reduce DNA laddering and the number of apoptotic nuclei. Staurosporine treatment also evokes apoptosis in human neuroblastoma SH-SY5Y. While Z-D-DCB is again anti-apoptotic, calpain inhibitors only provide modest effects in this model. Our results suggest that ICE-like protease plays a critical role in neuronal apoptosis whereas the contributions of calpain are more cell-type dependent.
Nath
R
R
Department of Neuroscience Therapeutics, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.
Raser
K J
KJ
McGinnis
K
K
Nadimpalli
R
R
Stafford
D
D
Wang
K K
KK
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000201:enzymology / Q000473:pathology; D002154:Calpain / Q000037:antagonists & inhibitors*; D020170:Caspase 1; D004396:Coloring Agents; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009447:Neuroblastoma / Q000201:enzymology / Q000473:pathology; D009474:Neurons / Q000187:drug effects*; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D014407:Tumor Cells, Cultured
D004396:Coloring Agents; D011480:Protease Inhibitors; D007770:L-Lactate Dehydrogenase; D002154:Calpain; D003546:Cysteine Endopeptidases; D020170:Caspase 1