Inhibitors of interleukin-1 beta-converting enzyme-family proteases (caspases) prevent apoptosis without affecting decreased cellular ability to reduce 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide in cerebellar granule neurons

Brain Research
J Harada, M Sugimoto

Abstract

We assessed the possible role of interleukin-1beta-converting enzyme-family proteases (caspases) in apoptosis in cultured rat cerebellar granule neurons. CPP32 (caspase-3)-like protease activity was augmented by low KCl treatment, preceding neuronal cell death. Agents such as brain-derived neurotrophic factor (BDNF), dibutylyl cAMP, NMDA, actinomycin D, S-adenosyl-L-methionine, and spermine prevented apoptosis. For various neuroprotective agents, the degree of apoptosis prevention correlated with the prevention of the activation of CPP32-like protease. Furthermore, Z-Asp-2, 6-dichlorobenzoyloxy-methylketone (Z-Asp-CH2-DCB), Boc-Asp-fluoromethylketone (Boc-Asp-FMK), and Z-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK), which are inhibitors of caspases, also prevented apoptosis. In contrast to many other neuroprotective agents, these inhibitors of caspases showed little effect on the decrease of cellular 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) reduction activity after low KCl treatment. The neurons rescued by these inhibitors of caspases during low KCl treatment were in a hypoenergic state in their ATP levels and vulnerable to subsequent treatment with medium containing high KCl or glutamate which induce a...Continue Reading

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Citations

Aug 15, 2000·European Journal of Pharmacology·G L WenkS Fiorucci
Jan 13, 2000·Neuropathology and Applied Neurobiology·J P SteinbachA Aguzzi
Feb 8, 2005·American Journal of Respiratory Cell and Molecular Biology·Stefanie KrickFrank Rose
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