JNK activation and up-regulation of thioredoxin reductase (TrxR) in the rat cochlea following styrene exposure.
Li-M; Chen-GD; Henderson-D
Abstr 32nd Midwinter Res Meet 2009 Feb; 32:202
Styrene, a widely used industrial chemical, is ototoxic. It causes death of auditory hair cells after about 7 days of exposure (800 mg/kg/day) through apoptosis (Chen et al., 2007). This study was designed to determine styreneinduced alterations in the cochlea underlying the apoptotic cell death. Thioredoxin(Trx)/thioredoxin reductase(TrxR) system plays an important role in maintaining cellular redox balance and inhibiting JNK pathway, which leads to apoptotic cell death. Long Evans rats were exposed to styrene by gavage at a dose of 800 mg/kg in oil for 4 days or as controls by oil gavage alone. Cochlear tissues were sampled 1 hour after the last exposure. TrxR and p-JNK were determined by Western blot analysis. The results showed a remarkable increase of p-JNK in the styrene exposed group compared to the oil control group. However, TrxR level in the styrene exposed level was also up-regulated. The data indicated that styrene did not cause damage to the Trx/TrxR redox system. We speculate that styrene exposure results in over-production of reactive oxygen species (ROS), which activates stress signaling pathways leading to apoptotic cell death. The over-produced ROS can also oxidize Trx and the overloaded oxidized Trx may stimulate synthesis of TrxR. This study was supported by NIOSH grant 1R01OH008113-01A1.
Noise-exposure; Exposure-levels; Noise-induced-hearing-loss; Noise-exposure; Noise; Hearing; Hearing-disorders; Hearing-loss; Laboratory-animals; Animals; Molecular-structure; Age-factors; Styrenes; Ototoxicity; Cell-damage
Abstracts of the 32nd Midwinter Research Meeting
Washington University, St. Louis