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Roles of NADPH oxidases in cisplatin-induced reactive oxygen species generation and ototoxicity.

ABSTRACT: In our previous study, we clearly demonstrated the roles of pro-inflammatory cytokines, including tumor necrosis factor-alpha, interleukin-1beta (IL-1beta), and IL-6, and subsequent reactive oxygen species (ROS) generation on the pathogenesis of cisplatin ototoxicity in vitro and in vivo. ROS generation in cisplatin-treated HEI-OC1 auditory cells was also correlated with changing mitochondrial membrane potential. However, the roles of NADPH oxidase in cisplatin-induced ROS generation and ototoxicity have not been fully elucidated. Herein, immunohistochemical studies demonstrated that treatment of cisplatin induced the expression of NADPH oxidase isoforms NOX-1 and NOX-4 in HEI-OC1 auditory cells. Expression of mRNA for NOX-1, NOX-4, NOXO1, NOXA1, p47(phox), and p67(phox) was also increased. Inhibition of NADPH oxidase with diphenyleniodonium chloride or apocynin abolished ROS production and the subsequent apoptotic cell death in cisplatin-treated cells. Furthermore, suppression of NOX1 and NOX4 expression by small interfering RNA transfection markedly abolished the cytotoxicity and ROS generation by cisplatin. Together, our data suggest that ROS generated, in part, through the activation of NADPH oxidase plays an essential role in cisplatin ototoxicity.

SUBMITTER: Kim HJ

PROVIDER: S-EPMC6632278 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Roles of NADPH oxidases in cisplatin-induced reactive oxygen species generation and ototoxicity.

Kim Hyung-Jin HJ Lee Jeong-Han JH Kim Se-Jin SJ Oh Gi Su GS Moon Hae-Dalma HD Kwon Kang-Beom KB Park Channy C Park Byung Hyun BH Lee Ho-Kyun HK Chung Sang-Young SY Park Raekil R So Hong-Seob HS

The Journal of neuroscience : the official journal of the Society for Neuroscience 20100301 11

In our previous study, we clearly demonstrated the roles of pro-inflammatory cytokines, including tumor necrosis factor-alpha, interleukin-1beta (IL-1beta), and IL-6, and subsequent reactive oxygen species (ROS) generation on the pathogenesis of cisplatin ototoxicity in vitro and in vivo. ROS generation in cisplatin-treated HEI-OC1 auditory cells was also correlated with changing mitochondrial membrane potential. However, the roles of NADPH oxidase in cisplatin-induced ROS generation and ototoxi ...[more]

PMID: 20237264

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Roles of NADPH oxidases in cisplatin-induced reactive oxygen species generation and ototoxicity.

Publications

Roles of NADPH oxidases in cisplatin-induced reactive oxygen species generation and ototoxicity.

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