The involvement of caspase-11 in TPEN-induced apoptosis

Abstract 

The depletion of intracellular zinc with N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) induces protein synthesis-dependent apoptosis. Here we examined the involvement of caspase induction in apoptosis. Among the examined caspases, only caspase-11 was increased by TPEN. Caspase-11 activity also increased, which resulted in caspase-3 activation. Cycloheximide or actinomycin D blocked caspase-11 induction, reduced caspase-11 and -3 activation, and attenuated TPEN-induced neuronal apoptosis. Blockade of caspase-11 by a chemical inhibitor or genetic deletion attenuated TPEN-induced apoptosis, indicating a critical role of caspase-11 in TPEN-induced apoptosis. Although mitochondria-mediated caspase-9/-3 activation also contributed to TPEN-induced apoptosis, caspase-11 is likely a key inducible apoptosis-inducing protein.

Abbreviations: TPEN, N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine, CHX, cycloheximide, ActD, actinomycin D, LDH, lactate dehydrogenase, PI, propidium iodide, DIV, days in vitro, MEFs, mouse embryonic fibroblasts, MPT, mitochondrial potential transition

Keywords: Zinc, Caspase-3, Caspase-9, Cycloheximide, Actinomycin D, Cytochrome C