tailieunhanh - Báo cáo khoa học: Autophagy inhibits reactive oxygen species-mediated apoptosis via activating p38-nuclear factor-kappa B survival pathways in oridonin-treated murine fibrosarcoma L929 cells

Autophagy and apoptosis have been known to be interconnected positively or negatively; however, the molecular mechanisms mediating these two cel-lular processes are not fully understood. In the present study, we demon-strated that the exposure of L929 cells to oridonin led to intracellular reactive oxygen species generation, followed by lipid peroxidation, as well as decreases in superoxide dismutase and glutathione activities. | ỊFEBS Journal Autophagy inhibits reactive oxygen species-mediated apoptosis via activating p38-nuclear factor-kappa B survival pathways in oridonin-treated murine fibrosarcoma L929 cells Yan Cheng1 2 Feng Qiu2 Yuan-Chao Ye1 Zhao-Ming Guo1 Shin-Ichi Tashiro3 Satoshi Onodera3 and Takashi Ikejima1 1 China-Japan Research Institute of Medicaland PharmaceuticalSciences Shenyang PharmaceuticalUniversity China 2 Department of NaturalProducts Chemistry Shenyang PharmaceuticalUniversity China 3 Department of Clinicaland BiomedicalSciences Showa PharmaceuticalUniversity Tokyo Japan Keywords apoptosis autophagy murine fibrosarcoma L929 cells oridonin ROS Correspondence T. Ikejima China-Japan Research Institute of Medical and Pharmaceutical Sciences Shenyang PharmaceuticalUniversity Shenyang 110016 China Fax 86 24 23844463 Tel 86 24 23844463 E-mail ikejimat@ Received 4 September 2008 revised 10 December 2008 accepted 18 December 2008 doi Autophagy and apoptosis have been known to be interconnected positively or negatively however the molecular mechanisms mediating these two cellular processes are not fully understood. In the present study we demonstrated that the exposure of L929 cells to oridonin led to intracellular reactive oxygen species generation followed by lipid peroxidation as well as decreases in superoxide dismutase and glutathione activities. The reactive oxygen species scavenger N-acetyl-cysteine resulted in the complete inhibition of oridonin-induced apoptosis and mitochondrial membrane potential collapse. We showed that reactive oxygen species triggered apoptosis by Bax translocation cytochrome c release and extracellular signal-regulated kinase activation. Further data confirmed that oridonin also induced L929 cell autophagy as demonstrated by extensive autophagic vacuolization and the punctuate distribution of monodansylcadaverine staining and GFP-LC3 as well as the LC3-H LC3-I proportion and Beclin 1 activation. .

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