Inhibition of caspase-3 processing by Z-DQMD-FMK (Z-Asp(OMe)-Gln-Met-Asp(OMe)-fluoromethylketone) did not restore cell number in the zinc-deficient group, but resulted in processing of full-length PKC-δ to a 56-kDa fragment1.
The inhibitory effect of specific caspase inhibitors (Z-DQMD-FMK, Z-IETD-FMK and Z-LEHD-FMK) suggests that the MG132-induced apoptotic cell death and depletion of GSH in SCLC cells are mediated by both activation of caspase-8 and mitochondrial damage, leading to the activation of caspase-9 and -32.
To investigate whether εPKC cleavage after stroke is caused by caspase-3 activation, we examined the effect of a cell-permeable caspase-3–specific inhibitor, Z-DQMD-FMK, on generation of cleaved εPKC fragments. Caspase-3 inhibition did not suppress the decrease in fulllength εPKC and the 43-kDa fragment in the ischemic core and penumbra after stroke3.
References:
1. Susan S. CHOU*, Michael S. CLEGG, Alterations in protein kinase C activity and processing during zinc-deficiency-induced cell death, Biochem. J. (2004) 383, 63–71
2. J. H. Banga, E. S. Han. Differential response of MG132 cytotoxicity against small cell lung cancer cells to changes in cellular GSH contents. Biochemical Pharmacology 68 (2004) 659–666.
3. T. Shimohata, H. Zhao, εPKC May Contribute to the Protective Effect of Hypothermia in a Rat Focal Cerebral Ischemia Model. Stroke. 2007;38:375-380