Bim mediates mitochondria-regulated particulate matter-induced apoptosis in alveolar epithelial cells.
We studied the role of Bim, a pro-apoptotic BCL-2 family member in Airborne particulate matter (PM 2.5 microm)-induced apoptosis in alveolar epithelial cells (AEC). PM induced AEC apoptosis by causing significant reduction of mitochondrial membrane potential and increase in caspase-9, caspase-3 and PARP-1 activation. PM upregulated pro-apoptotic protein Bim and enhanced translocation of Bim to the mitochondria. ShRNABim blocked PM-induced apoptosis by preventing activation of the mitochondrial death pathway suggesting a role of Bim in the regulation of mitochondrial pathway in AEC. Accordingly, we provide the evidence that Bim mediates PM-induced apoptosis via mitochondrial pathway.
Zhang
J
J
Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305-5236, USA.
Ghio
A J
AJ
Chang
W
W
Kamdar
O
O
Rosen
G D
GD
Upadhyay
D
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D002417:Cattle; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D052638:Particulate Matter / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects
D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606778:Bcl2l11 protein, rat; D008565:Membrane Proteins; D052638:Particulate Matter; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D011065:Poly(ADP-ribose) Polymerases
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