Humanin decreases mitochondrial membrane permeability by inhibiting the membrane association and oligomerization of Bax and Bid proteins
文献类型：期刊论文
| 作者 | Ma, Ze-wei1,2; Liu, Dong-xiang1,2
|
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2018-06 |
| 卷号 | 39期号:6页码:1012-1021 |
| 关键词 | Alzheimer's disease humanin Bcl-2 family mitochondrial outer membrane single-molecule fluorescence |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2017.169 |
| 文献子类 | Article |
| 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 A beta 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 Forster 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. |
| WOS关键词 | DISEASE-RELEVANT INSULTS ; RESCUE FACTOR HUMANIN ; NEURONAL CELL-DEATH ; ALZHEIMERS-DISEASE ; NEUROPROTECTIVE FACTOR ; COGNITIVE IMPAIRMENT ; MEMORY IMPAIRMENT ; INDUCE APOPTOSIS ; PEPTIDE HUMANIN ; CASPASE 8 |
| 资助项目 | National Natural Science Foundation of China[21472206] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:6264825 |
| WOS记录号 | WOS:000434380400012 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279726]  |
| 专题 | 药理学第三研究室 |
| 通讯作者 | Liu, Dong-xiang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Pharmacol 3, Key Lab Receptor Res, Shanghai 201203, Peoples R China; 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ma, Ze-wei,Liu, Dong-xiang. Humanin decreases mitochondrial membrane permeability by inhibiting the membrane association and oligomerization of Bax and Bid proteins[J]. ACTA PHARMACOLOGICA SINICA,2018,39(6):1012-1021. |
| APA | Ma, Ze-wei,&Liu, Dong-xiang.(2018).Humanin decreases mitochondrial membrane permeability by inhibiting the membrane association and oligomerization of Bax and Bid proteins.ACTA PHARMACOLOGICA SINICA,39(6),1012-1021. |
| MLA | Ma, Ze-wei,et al."Humanin decreases mitochondrial membrane permeability by inhibiting the membrane association and oligomerization of Bax and Bid proteins".ACTA PHARMACOLOGICA SINICA 39.6(2018):1012-1021. |
入库方式： OAI收割
来源：上海药物研究所
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