cGMP-Prkg1 signaling and Pde5 inhibition shelter cochlear hair cells and hearing function | Zendy

Mirko Jaumann | Zendy; Juliane Dettling | Zendy; Martin Gubelt | Zendy; Ulrike Zimmermann | Zendy; Andrea Gerling | Zendy; François Paquet-Durand | Zendy; Susanne Feil | Zendy; Samuel M. Wolpert | Zendy; Christoph Franz | Zendy; Ksenya Varakina | Zendy; Hao Xiong | Zendy; N. J. Brandt | Zendy; Stephanie Kuhn | Zendy; H Geisler | Zendy; Karin Rohbock | Zendy; Peter Ruth | Zendy; Jens Schlossmann | Zendy; Joachim Hütter | Zendy; Peter Sandner | Zendy; Robert Feil | Zendy; Jutta Engel | Zendy; Marlies Knipper | Zendy; Lukas Rüttiger | Zendy

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cGMP-Prkg1 signaling and Pde5 inhibition shelter cochlear hair cells and hearing function

Author(s) -

Mirko Jaumann,

Juliane Dettling,

Martin Gubelt,

Ulrike Zimmermann,

Andrea Gerling,

François Paquet-Durand,

Susanne Feil,

Samuel M. Wolpert,

Christoph Franz,

Ksenya Varakina,

Hao Xiong,

N. J. Brandt,

Stephanie Kuhn,

H Geisler,

Karin Rohbock,

Peter Ruth,

Jens Schlossmann,

Joachim Hütter,

Peter Sandner,

Robert Feil,

Jutta Engel,

Marlies Knipper,

Lukas Rüttiger

Publication year - 2012

Publication title -

nature medicine

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 19.536

H-Index - 547

eISSN - 1546-170X

pISSN - 1078-8956

DOI - 10.1038/nm.2634

Subject(s) - vardenafil , spiral ganglion , cyclic guanosine monophosphate , protein kinase a , gene knockdown , hair cell , microbiology and biotechnology , downregulation and upregulation , noise induced hearing loss , biology , signal transduction , phosphodiesterase , hearing loss , chemistry , kinase , cochlea , endocrinology , medicine , apoptosis , enzyme , biochemistry , gene , anatomy , sildenafil , nitric oxide , noise exposure , audiology , tadalafil

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 I (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.

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