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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2015.4
- 수록면
- 312 - 317 (6page)
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Depletion of intracellular zinc by N,N,N ,N -tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) induces p53-mediated protein synthesis-dependent apoptosis of mouse cortical neurons. Here, we examined the requirement for poly(ADPribose) polymerase (PARP)-1 as an upstream regulator of p53 in zinc depletion-induced neuronal apoptosis. First, we found that chemical inhibition or genetic deletion of PARP-1 markedly attenuated TPEN-induced apoptosis of cultured mouse cortical neurons. Poly(ADP-ribosyl)ation of p53 occurred starting 1 h after TPEN treatment. Suggesting the critical role of PARP-1, the TPEN-induced increase of stability and activity of p53 as well as poly(ADP-ribosyl)ation of p53 was almost completely blocked by PARP inhibition.
Consistent with this, the induction of downstream proapoptotic proteins PUMA and NOXA was noticeably reduced by chemical inhibitors or genetic deletion of PARP-1.
TPEN-induced cytochrome C release into the cytosol and caspase-3 activation were also blocked by inhibition of PARP-1. Taken together, these findings indicate that PARP- 1 is essential for TPEN-induced neuronal apoptosis.
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참고문헌 (37)
참고문헌 신청
Ahn, Y. H. / 1998 / Depletion of intracellular zinc induces protein synthesis-dependent neuronal apoptosis in mouse cortical culture / Exp. Neurol 154:47~56
Appella, E. / 2001 / Post-translational modifications and activation of p53 by genotoxic stresses / Eur. J. Biochem 268:2764~2772
Berger, N. A. / 1985 / Poly(ADP-ribose)in the cellular response to DNA damage / Radiat. Res 101:4~15
Berger, N. A. / 1985 / Identification of minimal size requirements of DNA for activation of poly(ADP-ribose)polymerase / Biochemistry 24:4352~4355
Blagosklonny, M. V. / 1997 / Loss of function and p53 protein stabilization / Oncogene 15:1889~1893
Appella, E. / 2001 / Post-translational modifications and activation of p53 by genotoxic stresses / Eur. J. Biochem 268:2764~2772
Berger, N. A. / 1985 / Poly(ADP-ribose)in the cellular response to DNA damage / Radiat. Res 101:4~15
Berger, N. A. / 1985 / Identification of minimal size requirements of DNA for activation of poly(ADP-ribose)polymerase / Biochemistry 24:4352~4355
Blagosklonny, M. V. / 1997 / Loss of function and p53 protein stabilization / Oncogene 15:1889~1893
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