The involvement of caspase-11 in TPEN-induced apoptosis.
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.
Lee
Jong-Min
JM
Department of Molecular Biology, Sejong University, 98 Gunja-Dong Gwangjin-Gu, Seoul 143-747, South Korea.
Kim
Yu-Jin
YJ
Ra
Hana
H
Kang
Shin-Jung
SJ
Han
Seungjin
S
Koh
Jae-Young
JY
Kim
Yang-Hee
YH
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D053471:Caspases, Initiator; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004789:Enzyme Activation; D005029:Ethylenediamines / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D034741:RNA, Small Interfering / Q000235:genetics; D015032:Zinc / Q000378:metabolism*
D061945:Caspase Inhibitors; D002614:Chelating Agents; D005029:Ethylenediamines; D034741:RNA, Small Interfering; D003609:Dactinomycin; D003513:Cycloheximide; C101136:Casp4 protein, mouse; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; D053471:Caspases, Initiator; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine