humanindecreasesmitochondrialmembranepermeabilitybyinhibitingthemembraneassociationandoligomerizationofbaxandbidproteins
文献类型：期刊论文
| 作者 | Ma Zewei; Liu Dongxiang
|
| 刊名 | actapharmacologicasinica
 |
| 出版日期 | 2018 |
| 卷号 | 039期号:006页码:1012 |
| 关键词 | Bax 膜渗透 蛋白质 协会 apoptosis 类脂化合物 单个分子 细胞色素 |
| ISSN号 | 1671-4083 |
| 英文摘要 | Humanin （HN） is a 24-residue peptide identified from the brain of a patient with Alzheimer＇s disease （AD）. HN has been found to protect against neuronal insult caused by Aβ peptides or transfection of familial AD mutant genes. In order to elucidate the molecular mechanisms of HN neuroprotection, we explored the effects of HN on the association of Bax or Bid with lipid bilayers and their oligomerization in the membrane. By using single-molecule fluorescence and F6rster resonance energy transfer techniques, we showed that Bax was mainly present as monomers, dimers and tetramers in lipid bilayers, while truncated Bid （tBid） enhanced the membrane association and tetramerization of Bax. HN （100 nmol/L） inhibited the self-association and tBid-activated association of Bax with the bilayers, and significantly decreased the proportion of Bax in tetramers. Furthermore, HN inhibited Bid translocation to lipid bilayers. HN could bind with Bax and Bid either in solution or in the membrane. However, HN could not pull the proteins out of the membrane. Based on these results, we propose that HN binds to Bax and cBid in solution and inhibits their translocation to the membrane. Meanwhile, HN interacts with the membrane-bound Bax and tBid, preventing the recruitment of cytosolic Bax and its oligomerization in the membrane. In this way, HN inhibits Bax pore formation in mitochondrial outer membrane and suppresses cytochrome c release and mitochondria-dependent apoptosis. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/286489]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 中国科学院上海药物研究所 |
| 推荐引用方式 GB/T 7714 | Ma Zewei,Liu Dongxiang. humanindecreasesmitochondrialmembranepermeabilitybyinhibitingthemembraneassociationandoligomerizationofbaxandbidproteins[J]. actapharmacologicasinica,2018,039(006):1012. |
| APA | Ma Zewei,&Liu Dongxiang.(2018).humanindecreasesmitochondrialmembranepermeabilitybyinhibitingthemembraneassociationandoligomerizationofbaxandbidproteins.actapharmacologicasinica,039(006),1012. |
| MLA | Ma Zewei,et al."humanindecreasesmitochondrialmembranepermeabilitybyinhibitingthemembraneassociationandoligomerizationofbaxandbidproteins".actapharmacologicasinica 039.006(2018):1012. |
入库方式： OAI收割
来源：上海药物研究所
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