ASPP2 involvement in p53-mediated HIV-1 envelope glycoprotein gp120 neurotoxicity in mice cerebrocortical neurons.
ASPP2 involvement in p53-mediated HIV-1 envelope glycoprotein gp120 neurotoxicity in mice cerebrocortical neurons.
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ASPP2参与p53介导的HIV-1包膜糖蛋白gp120对小鼠大脑皮质神经元的神经毒性
DOI:
10.1038/srep33378
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发表时间:
2016-09-14
影响因子:
4.6
通讯作者:
Chen D
中科院分区:
文献类型:
--
作者:
Liu Z;Zang Y;Qiao L;Liu K;Ouyang Y;Zhang Y;Chen D
The mechanisms behind HIV-1-associated neurocognitive disorders are still unclear. Apoptosis-stimulating protein 2 of p53 (ASPP2) is a damage-inducible p53-binding protein that stimulates p53-mediated apoptosis and transactivates proapoptotic and cell cycle regulatory genes. It has been reported that ASPP2 has a specific regulatory function in the death of retinal ganglion cells and the development of Alzheimer’s disease. In this study, we used p53 and ASPP2 knockout mice and primary cerebrocortical neuron culture to analyze the role of the interaction between ASPP2 with p53 in HIV-1 envelope glycoprotein gp120-induced neurotoxicity. The results showed that 10 ng/mL gp120 protein might stimulate p53 overexpression and translocation to the nucleus, and 30 ng/mL gp120 protein could stimulate both p53 and ASPP2 translocation to the nucleus, but only with p53 overexpression. The primary cultured neurons of p53−/−ASPP2+/−mice had a higher survival rate than p53−/−mice under gp120 protein stress. The interaction of ASPP2 with p53 induced by a high dose of gp120 stimulated Bax transcription and contributed to caspase-3 cleavage, and ASPP2-siRNA attenuated gp120 induced neuron death through inhibition of Bax expression. These results suggest that ASPP2 plays an important role in p53-mediated neuronal apoptosis under gp120 stress.
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影响因子:
14.9
作者:
Christmann M;Kaina B
通讯作者:
Kaina B
影响因子:
13.6
作者:
Dai C;Gu W
通讯作者:
Gu W
影响因子:
3.3
作者:
Louboutin JP;Agrawal L;Reyes BA;van Bockstaele EJ;Strayer DS
通讯作者:
Strayer DS
影响因子:
6.2
作者:
Podhaizer, Elizabeth M.;Zou, Shiping;Fitting, Sylvia;Samano, Kimberly L.;El-Hage, Nazira;Knapp, Pamela E.;Hauser, Kurt F.
通讯作者:
Hauser, Kurt F.
影响因子:
8
作者:
Pietsch, E. C.;Sykes, S. M.;McMahon, S. B.;Murphy, M. E.
通讯作者:
Murphy, M. E.