Essential role of p53 in TPEN-induced neuronal apoptosis

Hana Ra; Hyun Lim Kim; Han Woong Lee; Yang Hee Kim

doi:10.1016/j.febslet.2009.04.008

Essential role of p53 in TPEN-induced neuronal apoptosis

Hana Ra, Hyun Lim Kim, Han Woong Lee, Yang Hee Kim

Research output: Contribution to journal › Article › peer-review

28 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1516-1520
Number of pages	5
Journal	FEBS Letters
Volume	583
Issue number	9
DOIs	https://doi.org/10.1016/j.febslet.2009.04.008
Publication status	Published - 2009 May 6

Bibliographical note

Funding Information:
This study was supported by grants from the Korea Science & Engineering Foundation (KOSEF) (M10412000012-07N1200-01210 and R01-2006-000-10771-0(2008)).

All Science Journal Classification (ASJC) codes

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

Access to Document

10.1016/j.febslet.2009.04.008

Cite this

@article{63cc7b4385b9403384f92e17343b23a2,

title = "Essential role of p53 in TPEN-induced neuronal apoptosis",

abstract = "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.",

author = "Hana Ra and Kim, {Hyun Lim} and Lee, {Han Woong} and Kim, {Yang Hee}",

note = "Funding Information: This study was supported by grants from the Korea Science & Engineering Foundation (KOSEF) (M10412000012-07N1200-01210 and R01-2006-000-10771-0(2008)).",

year = "2009",

month = may,

day = "6",

doi = "10.1016/j.febslet.2009.04.008",

language = "English",

volume = "583",

pages = "1516--1520",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "Elsevier",

number = "9",

}

TY - JOUR

T1 - Essential role of p53 in TPEN-induced neuronal apoptosis

AU - Ra, Hana

AU - Kim, Hyun Lim

AU - Lee, Han Woong

AU - Kim, Yang Hee

N1 - Funding Information: This study was supported by grants from the Korea Science & Engineering Foundation (KOSEF) (M10412000012-07N1200-01210 and R01-2006-000-10771-0(2008)).

PY - 2009/5/6

Y1 - 2009/5/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=67349088722&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67349088722&partnerID=8YFLogxK

U2 - 10.1016/j.febslet.2009.04.008

DO - 10.1016/j.febslet.2009.04.008

M3 - Article

C2 - 19364507

AN - SCOPUS:67349088722

SN - 0014-5793

VL - 583

SP - 1516

EP - 1520

JO - FEBS Letters

JF - FEBS Letters

IS - 9

ER -

Essential role of p53 in TPEN-induced neuronal apoptosis

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this