humanindecreasesmitochondrialmembranepermeabilitybyinhibitingthemembraneassociationandoligomerizationofbaxandbidproteins

	humanindecreasesmitochondrialmembranepermeabilitybyinhibitingthemembraneassociationandoligomerizationofbaxandbidproteins
	Ma Zewei; Liu Dongxiang
刊名	actapharmacologicasinica
	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
内容类型	期刊论文
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.