title: Noise induces A1 adenosine receptor expression in the chinchilla cochlea.
abstract: Adenosine plays a major cytoprotective role during ischemia and conditions of oxidative stress. Previous studies in our laboratory indicate that oxidative stress induces expression of the A1 adenosine receptor (A1AR) via activation of nuclear factor (NF)-kappaB. In this study, we tested whether noise exposure could induce oxidative stress and determine whether this induces expression of the A1AR in the chinchilla cochlea. Chinchillas were exposed to a 96 dB 4 kHz octave band of noise for 6 h of daily exposure, followed by an 18 h noise-free period. This noise paradigm resulted in threshold shifts of 10-60 dB over the frequency range (1-16 kHz) tested. Radioligand binding studies for the A1AR indicate a significant increase in receptor ( approximately 2-fold) expression soon after the first noise exposure period (usually within approximately 8 h of the initiation of noise), which gradually returned to basal levels by day 7. The rise in A1AR levels was followed by a significant increase in malondialdehyde levels by day 3, which also recovered by day 7. Assessment of the activity of NADPH oxidase in the cochlea indicates a significant increase in enzyme activity which was evident by approximately 8 h following initiation of noise exposure, and which persisted for at least up to day 3. Electrophoretic mobility shift assays indicate that the increase in A1AR was associated with a significant increase in NF-kappaB activity following noise exposure. We conclude that noise exposure induces A1AR expression, which might be mediated, in part, through generation of reactive oxygen species and activation of NF-kappaB.
authors.affiliation: Department of Pharmacology, Southern Illinois University School of Medicine, P.O. Box 19620, Springfield, IL 62794-9620, USA. bramkumar@siumed.edu
authors.forename: Vickram
authors.initials: V
authors.lastname: Ramkumar
authors.forename: Craig A
authors.initials: CA
authors.lastname: Whitworth
authors.forename: Sandeep C
authors.initials: SC
authors.lastname: Pingle
authors.forename: Larry F
authors.initials: LF
authors.lastname: Hughes
authors.forename: Leonard P
authors.initials: LP
authors.lastname: Rybak
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001300:Audiometry, Evoked Response; D002682:Chinchilla; D003051:Cochlea / Q000201:enzymology / Q000378:metabolism*; D016057:Evoked Potentials, Auditory, Brain Stem; D006317:Hearing Loss, Noise-Induced / Q000378:metabolism* / Q000503:physiopathology; D015227:Lipid Peroxidation; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009622:Noise / Q000009:adverse effects*; D018384:Oxidative Stress / Q000502:physiology; D011869:Radioligand Assay; D017382:Reactive Oxygen Species / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species; D018047:Receptors, Purinergic P1; D019255:NADPH Oxidases; D000241:Adenosine