S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3  

作　　者：Saeid Ghavami Mehdi Eshragi Sudharsana R Ande Walter J Chazin Thomas Klonisch Andrew J Halayko Karol D Mcneill Mohammad Hashemi Claus Kerkhoff Marek Los 

机构地区：[1]Department of Biochemistry and Medical Genetics, Manitoba Institute of Cell Biology, CancerCare Manitoba, Winnipeg, Canada [2]Department of Physiology, University of Manitoba, Winnipeg, Canada [3]Manitoba Institute of Child Health, University of Manitoba, Winnipeg, Canada [4]Department of Biochemistry and Chemistry, Center for Structural Biology, Vanderbilt University, Nashville, TN 37232-8725, USA [5]Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Canada [6]Department of Clinical Biochemistry, Zahedan University of Medical Sciences, Zahedan [7]Institute of Immunology, University of Muenster, Roentgenstr. 21, Muenster, Germany [8]Interfaculty Institute of Biochemistry, University of Tiibingen, Hoppe-Seyler-Street 4/401B, Tiibingen, Germany

出　　处：《Cell Research》2010年第3期314-331,共18页细胞研究（英文版）

摘　　要：The complex formed by two members of the S100 calcium-binding protein family, S100A8/A9, exerts apoptosisinducing 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 Atgl2-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, ATM-BNIP3 overexpression partially inhibited S100A8/A9-induced cell death, decreased reactive oxygen species （ROS） generation, and partially pro- tected against the decrease in mitochondrial transmembrane potential in S100A8/A9-treated ceils. In addition, either ATM-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.

关 键 词：S100A8/A9 CALPROTECTIN lysosomal activation mitochondrial membrane potential BNIP3 BECLIN-1 

分 类 号：Q244[生物学—细胞生物学] Q255