Jaumann, Mirko and Dettling, Juliane and Gubelt, Martin and Zimmermann, Ulrike and Gerling, Andrea and Paquet-Durand, Francois and Feil, Susanne and Wolpert, Stephan and Franz, Christoph and Varakina, Ksenya and Xiong, Hao and Brandt, Niels and Kuhn, Stephanie and Geisler, Hyun-Soon and Rohbock, Karin and Ruth, Peter and Schlossmann, Jens and Huetter, Joachim and Sandner, Peter and Feil, Robert and Engel, Jutta and Knipper, Marlies and Ruettiger, Lukas (2012) cGMP-Prkg1 signaling and Pde5 inhibition shelter cochlear hair cells and hearing function. NATURE MEDICINE, 18 (2). pp. 252-259. ISSN 1078-8956,
Full text not available from this repository. (Request a copy)Abstract
Noise-induced hearing loss (NIHL) is a global health hazard with considerable pathophysiological and social consequences that has no effective treatment. In the heart, lung and other organs, cyclic guanosine monophosphate (cGMP) facilitates protective processes in response to traumatic events. We therefore analyzed NIHL in mice with a genetic deletion of the gene encoding cGMP-dependent protein kinase type 1 (Prkg1) and found a greater vulnerability to and markedly less recovery from NIHL in these mice as compared to mice without the deletion. Prkg1 was expressed in the sensory cells and neurons of the inner ear of wild-type mice, and its expression partly overlapped with the expression profile of cGMP-hydrolyzing phosphodiesterase 5 (Pde5). Treatment of rats and wild-type mice with the Pde5 inhibitor vardenafil almost completely prevented NIHL and caused a Prkg1-dependent upregulation of poly (ADP-ribose) in hair cells and the spiral ganglion, suggesting an endogenous protective cGMP-Prkg1 signaling pathway that culminates in the activation of poly (ADP-ribose) polymerase. These data suggest vardenafil or related drugs as possible candidates for the treatment of NIHL.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GUINEA-PIG COCHLEA; DEPENDENT PROTEIN-KINASE; P2X(2) RECEPTOR SUBUNIT; NITRIC-OXIDE SYNTHASE; CYCLIC-GMP; STEREOCILIA DAMAGE; POTASSIUM CURRENT; INNER-EAR; CGMP; PHOSPHODIESTERASE; |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann, formerly Prof. Seifert) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 May 2020 05:37 |
| Last Modified: | 20 May 2020 05:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19314 |
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