S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3.
S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3.
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作者：
由S100钙结合蛋白家族的两个成员S100 A8/A9形成的复合物在不同来源的各种细胞中发挥凋亡诱导活性。在这里，我们提出的证据表明，潜在的分子机制涉及程序性细胞死亡I（PCD I，凋亡）和PCD II（自噬）样死亡。用S100 A8/A9处理细胞引起Beclin-1表达增加以及Atg 12-Atg 5形成。S100 A8/A9诱导的细胞死亡被特异性PI 3-激酶III类抑制剂3-甲基腺嘌呤（3-MA）和空泡H+-ATP酶抑制剂巴菲霉素-A1（Baf-A1）部分抑制。S100 A8/A9引起BNIP 3（仅BH 3促凋亡Bcl 2家族成员）易位至线粒体。与这一发现一致，Δ TM-BNIP 3过表达部分抑制S100 A8/A9诱导的细胞死亡，减少活性氧（ROS）的产生，并部分保护S100 A8/A9处理的细胞免受线粒体跨膜电位降低的影响。此外，Δ TM-BNIP 3过表达或N-乙酰基-L-半胱氨酸共处理降低了用S100 A8/A9处理的细胞中的溶酶体活化。我们的数据表明，S100 A8/A9促进的细胞死亡通过ROS与线粒体和溶酶体的相互作用发生，该过程涉及BNIP 3。
The complex formed by two members of the S100 calcium-binding protein family, S100A8/A9, exerts apoptosis-inducing activity in various cells of different origins. Here, we present evidence that the underlying molecular mechanisms involve both programmed cell death I (PCD I, apoptosis) and PCD II (autophagy)-like death. Treatment of cells with S100A8/A9 caused the increase of Beclin-1 expression as well as Atg12-Atg5 formation. S100A8/A9-induced cell death was partially inhibited by the specific PI3-kinase class III inhibitor, 3-methyladenine (3-MA), and by the vacuole H+-ATPase inhibitor, bafilomycin-A1 (Baf-A1). S100A8/A9 provoked the translocation of BNIP3, a BH3 only pro-apoptotic Bcl2 family member, to mitochondria. Consistent with this finding, ΔTM-BNIP3 overexpression partially inhibited S100A8/A9-induced cell death, decreased reactive oxygen species (ROS) generation, and partially protected against the decrease in mitochondrial transmembrane potential in S100A8/A9-treated cells. In addition, either ΔTM-BNIP3 overexpression or N-acetyl-L-cysteine co-treatment decreased lysosomal activation in cells treated with S100A8/A9. Our data indicate that S100A8/A9-promoted cell death occurs through the cross-talk of mitochondria and lysosomes via ROS and the process involves BNIP3.
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影响因子：
5.3
作者：
Ghavami S;Asoodeh A;Klonisch T;Halayko AJ;Kadkhoda K;Kroczak TJ;Gibson SB;Booy EP;Naderi-Manesh H;Los M
通讯作者：
Los M
影响因子：
4.8
作者：
Kerkhoff, C;Nacken, W;Doussiere, J
通讯作者：
Doussiere, J
DOI：
10.1016/s0167-4889(98)00144-x
发表时间：
1998-12-10
影响因子：
5.1
作者：
Kerkhoff, C;Klempt, M;Sorg, C
通讯作者：
Sorg, C
影响因子：
5.3
作者：
Burton, Teralee R.;Eisenstat, David D.;Gibson, Spencer B.
通讯作者：
Gibson, Spencer B.
DOI：
10.1016/j.bbamcr.2007.10.015
发表时间：
2008-02-01
影响因子：
5.1
作者：
Ghavami, Saeld;Kerkhoff, Claus;Los, Marek
通讯作者：
Los, Marek