Essential role of p53 in TPEN-induced neuronal apoptosis.
Depletion of intracellular zinc with N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) induces protein synthesis-dependent apoptosis. In this study, we examined the requirement for p53 as an upstream transcription factor in TPEN-induced neuronal apoptosis. Chemical or genetic blockade of p53 markedly attenuated TPEN-induced neuronal apoptosis, while the stability and activity of p53 were increased by TPEN. In addition, expression of proapoptotic genes, PUMA and NOXA, and activation of caspase-11 were increased by TPEN in a p53-dependent manner. Inhibition of p53 blocked cytochrome C release from mitochondria to cytosol and prevented caspase-3 activation. Therefore, p53 may be an essential regulatory factor for TPEN-induced neuronal apoptosis.
Department of Molecular Biology, Sejong University, 98 Gunja-Dong Gwangjin-Gu, Seoul 143-747, South Korea.
Hana
H
Ra
Hyun-Lim
HL
Kim
Han-Woong
HW
Lee
Yang-Hee
YH
Kim
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D005029:Ethylenediamines / Q000494:pharmacology*; D007150:Immunohistochemistry; D051379:Mice; D018613:Microscopy, Confocal; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D017931:DNA Primers; D005029:Ethylenediamines; D016159:Tumor Suppressor Protein p53; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine