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Carbon Ion Beams Induce Hepatoma Cell Death by NADPH Oxidase‐Mediated Mitochondrial Damage
Author(s) -
Sun Chao,
Wang Zhenhua,
Liu Yang,
Liu Yuanyuan,
Li Hongyan,
Di Cuixia,
Wu Zhenhua,
Gan Lu,
Zhang Hong
Publication year - 2014
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24424
Subject(s) - nadph oxidase , mitochondrion , apocynin , reactive oxygen species , programmed cell death , microbiology and biotechnology , dna damage , mitochondrial ros , chemistry , biology , biochemistry , apoptosis , dna
Mitochondria are a major source of reactive oxygen species (ROS) and are also the target of cellular ROS. ROS damage to mitochondria leads to dysfunction that further enhances the production of mitochondrial ROS. This feed‐forward vicious cycle between mitochondria and ROS induces cell death. Within a few minutes of radiation exposure, NADPH oxidase is activated to elevate the ROS level. Activated NADPH oxidase might induce the feed‐forward cycle of mitochondria and this is a possible mechanism for cancer cell death induced by heavy ion irradiation. We found that after 4 Gy of 12 C 6+ ion radiation of HepG2 cells, the NADPH oxidase membrane subunit gp91 phox was not involved in enzyme activation through increased expression; however, the subunit p47 phox was involved in activation by being translocated to the membrane. 12 C 6+ ion radiation clearly decreased the ΔΨm of HepG2 cells, increasing mitochondrial DNA damage and inducing cell death. Pretreatment with apocynin (APO, an NADPH oxidase inhibitor) effectively prevented the ΔΨm decrease, mitochondrial DNA damage, and cell death induced by radiation. However, these protective effects were not observed with APO treatment after irradiation exposure. These data demonstrated that NADPH oxidase activation was an initiator in mitochondrial damage. Once mitochondria entered the feed‐forward cycle, cell fate was no longer controlled by NADPH oxidase. Only antioxidants that targeted mitochondria such as MitoQ could break the cycle and release cells from death. J. Cell. Physiol. 229: 100–107, 2014. © 2013 Wiley Periodicals, Inc.