The involvement of reactive oxygen species (ROS) and p38 mitogen‐activated protein (MAP) kinase in TRAIL/Apo2L‐induced apoptosis

FEBS Letters

Lee, Myoung-Woo¹  Park, Soon Cheol²  Bach, Jae-Hyung¹  Kim, Sung Su¹  Lee, Hyun Jung¹  Yim, Soon Ock⁴  Lee, Won Bok¹  Yang, Young Geun³  Chae, Hee Sun¹  Kim, Kyung Yong¹ 

[1] Department of Anatomy, College of Medicine, Chung-Ang University, 221 Huksuk-dong, Dongjak-ku, Seoul 156-756, South Korea;Department of Life Science, College of Natural Science, Chung-Ang University, 221 Huksuk-dong, Dongjak-ku, Seoul 156-756, South Korea;Biogrand Inc., Chung-Ang University, 221 Huksuk-dong, Dongjak-ku, Seoul 156-756, South Korea;School of Oriental Medicine, South Baylo University, Anaheim, CA, USA

关键词: Tumor necrosis factor-related apoptosis-inducing ligand;    Reactive oxygen species;    p38 mitogen-activated protein kinase;    Caspase;    Apoptosis;    TRAIL/Apo2L;    tumor necrosis factor-related apoptosis-inducing ligand;    DR;    death receptor;    ROS;    reactive oxygen species;    p38 MAP kinase;    p38 mitogen-activated protein kinase;    TNF;    tumor necrosis factor;    MTT;    3-(4;    5-dimethyl-thiozol-2-yl)-2;    5-diphenyl-tetrazolium bromide;    zVAD-fmk;    Z-Val-Ala-DL-Asp-fluoromethyl ketone;    GSH;    glutathione;   

DOI  :  10.1016/S0014-5793(02)02225-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

To determine the apoptotic signaling pathway which tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) induced, we investigated the contribution of reactive oxygen species (ROS), p38 mitogen-activated protein (MAP) kinase and caspases in human adenocarcinoma HeLa cells. Here we show that upon TRAIL/Apo2L exposure there was pronounced ROS accumulation and activation of p38 MAP kinase, and that activation of caspases and apoptosis followed. Pretreatment with antioxidants such as glutathione or estrogen attenuated TRAIL/Apo2L-induced apoptosis through a reduction of ROS generation and diminished p38 MAP kinase and caspase activation. The p38 MAP kinase inhibitor SB203580 prevented apoptosis through a blockage of caspase activation, although ROS generation was not attenuated. Furthermore, the pan-caspase inhibitor Z-Val-Ala-DL-Asp-fluoromethyl ketone fully prevented apoptosis, while neither ROS accumulation nor p38 MAP kinase activation were affected. Therefore, our results suggest that TRAIL/Apo2L-induced apoptosis is mediated by ROS-activated p38 MAP kinase followed by caspase activation in HeLa cells.

【 授权许可】

Unknown