Selective induction of catalase-mediated autophagy by dihydrocapsaicin in lung cell lines.
We reported that dihydrocapsaicin (DHC) induces autophagy in a catalase-regulated manner. In this study, we further examined the role of DHC-induced autophagy in lung cell lines. DHC-induced cytotoxicity was higher in WI38 and H1299 cells than in H460 and A549 cells, and was related to the loss of cell membrane integrity. However, apoptotic cells markedly increased in H460 and A549 cells. In WI38 and H1299 cells, DHC-induced catalase was correlated with a decrease of intracellular reactive oxygen species (ROS) and an increase in the level of LC3II, an autophagy marker, and LC3 conversion was attenuated by the catalase inhibitor 3-amino-1,2,4-triazole (3AT) or by knockdown of the catalase gene. In A549 cells, DHC downregulated catalase, led to ROS accumulation, and blocked LC3 conversion. In H460 cells expressing limited amount of catalase, DHC caused ROS accumulation and blocked LC3 conversion. However, H460 cells overexpressing catalase were able to induce autophagy. In contrast to Earle's balanced salt solution and rotenone, H(2)O(2) treatment caused ROS accumulation and did not promote upregulation of catalase and LC3II in lung cell lines. Cytoplasmic vacuolization in WI38 and H1299 cells was blocked by treatment of 3AT and which enhanced caspase-3 activity and LDH release. Suppression of autophagy by 3-methyladenine also enhanced DHC-induced cell death through apoptotic and necrotic cell death. In A549 and H460 cells, treatment of rapamycin attenuated DHC-induced cell death. Collectively, these results suggest that catalase regulates autophagy, which helps protect cells against apoptotic and necrotic cell death.
Choi
Cheol-Hee
CH
Research Center for Resistant Cells, College of Medicine, Chosun University, Seosuk-dong, Dong-gu, Gwangju 501-759, Korea.
Jung
Yong-Keun
YK
Oh
Seon-Hee
SH
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000640:Amitrole / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects / Q000235:genetics; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002374:Catalase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008168:Lung / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology
C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C025946:3-methyladenine; D002374:Catalase; D000225:Adenine; D002211:Capsaicin; D020123:Sirolimus; C012906:dihydrocapsaicin; D000640:Amitrole