Corticotropin-releasing factor-2 activation prevents gentamicin-induced oxidative stress in cells derived from the inner ear.

摘要: Numerous external agents, including high-intensity noise and various drugs, damage hair cells and/or support of the inner ear (Santi Duvall, 1978; Rybak, 1986; Huizing de Groot, 1987; Fredelius et al., 1990). Because mammalian do not regenerate, cytotoxic stress-induced can lead to significant hearing loss. Despite differences in initial targeted compartments by interactions ototoxic drugs damaging noise, these agents ultimately seem produce similar cellular pathologies likely have overlapping mechanisms action, perhaps activation same signaling pathways, that cell death (Kopke 1999). Metabolically induced noise-activated oxidative stress production reactive oxygen species (ROS) play a role cochlear injury (Yamane 1995). Given natural activity state ear, highly active endogenous defenses against initiation stress/damage must exist, yet little is known mechanisms. Indeed, most research date has focused on mitigating ROS-associated damage, despite fact presence elevated ROS levels indicates already taken place. That exist protect earliest phases exemplified efficacy sound-conditioning paradigms attenuating both noise-induced drug-induced loss (Canlon 1988; Campo 1991; Subramaniam 1992; Suryadevara 2009). Two effects sound conditioning suggested as underlying which protects are an increase antioxidant enzymes (Jacono 1998; Harris 2006; Henderson 2006) inhibition apoptosis (Niu 2003). Protective been reported last for long 60 days (McFadden 1997), suggesting involvement intracellular pathways. exposure initially nondamaging shown result nonetheless functional defects with aging (Kujawa Liberman, because also be effective temporary threshold shifts humans (Miyakita 1992), clearer more detailed definition involved protection fundamental only our understanding basic function, but designing future interventional strategies designed lessen deleterious following intense stimuli. We recognized constantly exposed stress-inducing stimuli, extent skin cope such impacts. Therefore, we modeled hypotheses concerning identity components making up response system skin. One expressed plays major stress-response involves corticotropin-releasing factor (CRF) its receptors (Slominski 1999, 2000, 2001). We previously express CRF, urocortin (a CRF-related peptide), CRF (Vetter 2002). demonstrated one receptors, CRF2, controlling auditory brainstem (ABR) thresholds establishing susceptibility permanent ABR (Graham 2010). Here define CRF2 aminoglycoside-induced generation associated go use global proteomics approach begin defining may explain ability provide protection. These preliminary protein data hold information potential novel therapeutic targets rational drug design useful combating compounds.