期刊
CELL RESEARCH
卷 20, 期 3, 页码 314-331出版社
INST BIOCHEMISTRY & CELL BIOLOGY
DOI: 10.1038/cr.2009.129
关键词
S100A8/A9; Calprotectin; lysosomal activation; mitochondrial membrane potential; BNIP3; Beclin-1
类别
资金
- MHRC
- MICH
- NTPAA
- CLA/CIHR/GSK
- University of Muenster [Ker3/086/04]
- Deutsche Forschungsgemeinschaft (DFG) [KE 820/6-1, KE 820/2-4]
- US National Institutes of Health [RO1 GM62112]
- CCMF
- Deutsche Forschungsgemeinschaft [SFB 773, GRK 1302]
- Deutsche Krebshilfe
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, Delta TM-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. TM-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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