Attenuated RhoA/Rho-kinase Signaling in Penis of Transgenic Sickle Cell Mice

Trinity J. Bivalacqua; Ashley E. Ross; Travis D. Strong; Milena A. Gebska; Biljana Musicki; Hunter C. Champion; Arthur L. Burnett

doi:10.1016/j.urology.2010.02.050

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Attenuated RhoA/Rho-kinase Signaling in Penis of Transgenic Sickle Cell Mice

Journal article

Peer reviewed

Attenuated RhoA/Rho-kinase Signaling in Penis of Transgenic Sickle Cell Mice

Trinity J. Bivalacqua, Ashley E. Ross, Travis D. Strong, Milena A. Gebska, Biljana Musicki, Hunter C. Champion and Arthur L. Burnett

Urology (Ridgewood, N.J.), Vol.76(2), pp.510.e7-510.e12

2010

DOI: 10.1016/j.urology.2010.02.050

PMCID: PMC3762569

PMID: 20538321

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https://www.ncbi.nlm.nih.gov/pmc/articles/3762569View

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Abstract

The Ras homolog gene family, member A (RhoA) and its main downstream effector, Rho-kinase (ROCK) are important in maintaining the penis in the flaccid state. The pathophysiology of sickle cell disease-associated priapism is not well defined. We hypothesized that the RhoA/ROCK vasoconstrictive pathways might be involved in the development of priapism. Therefore, the objective of the present study was to evaluate the molecular changes in RhoA and ROCK in an established transgenic sickle cell mouse model of priapism. Two groups of mice were used: wild type (WT; C57BL/6) mice and transgenic sickle cell mice. We evaluated RhoA guanosine triphosphatase and total ROCK activities, as well as ROCK1 and ROCK2 protein expression, in WT and sickle mice penises. We also evaluated the in vivo erectile responses to cavernous nerve stimulation and the frequency and duration of spontaneous erections before and after cavernous nerve stimulation. Sickle mice demonstrated significantly ( P <.05) enhanced erectile responses to cavernous nerve stimulation and frequency of spontaneous erections both before and after cavernous nerve stimulation compared with the WT mice. The sickle mice penises had a significant decline in RhoA guanosine triphosphatase ( P <.01) and total ROCK activities ( P <.05) compared with the WT mice. A significant (P <.05) reduction in ROCK2 protein expression in sickle mice penises compared with WT mice protein expression. No change in ROCK1 protein expression was observed in either cohort of mice penises. These data suggest that sickle cell disease associated-priapism might be contributed by a lack of RhoA/ROCK-mediated vasoconstriction and highlight a novel molecular mechanism in the pathophysiology of priapism.

Details

Title: Subtitle: Attenuated RhoA/Rho-kinase Signaling in Penis of Transgenic Sickle Cell Mice
Creators: Trinity J. Bivalacqua - Johns Hopkins University
Ashley E. Ross - Johns Hopkins University
Travis D. Strong - Johns Hopkins University
Milena A. Gebska - University of Iowa
Biljana Musicki - Johns Hopkins University
Hunter C. Champion - University of Pittsburgh Medical Center
Arthur L. Burnett - Johns Hopkins University
Resource Type: Journal article
Publication Details: Urology (Ridgewood, N.J.), Vol.76(2), pp.510.e7-510.e12
DOI: 10.1016/j.urology.2010.02.050
PMID: 20538321
PMCID: PMC3762569
NLM abbreviation: Urology
ISSN: 0090-4295
eISSN: 1527-9995
Publisher: Elsevier Inc
Grant note: American Urological Association Foundation Astellas U.S. Foundation RO1DK67223 / National Institute of Health U54HL90515 / Sickle Cell Program Project
Language: English
Date published: 2010
Academic Unit: Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984359584002771

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