Involvement of DDAH-ADMA-NOS-cGMP and COX-2-PTGIS-cAMP Pathways in Human Tissue Kallikrein 1 Protecting Erectile Function in Aged RatsReportar como inadecuado




Involvement of DDAH-ADMA-NOS-cGMP and COX-2-PTGIS-cAMP Pathways in Human Tissue Kallikrein 1 Protecting Erectile Function in Aged Rats - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Our previous studies had reported that Human Tissue Kallikrein 1 hKLK1 preserved erectile function in aged transgenic rats, while the detailed mechanism of hKLK1 protecting erectile function in aged rats through activation of cGMP and cAMP was not mentioned. To explore the latent mechanism, male wild-type Sprague-Dawley rats WTR and transgenic rats harboring the hKLK1 gene TGR were fed to 4 and 18 months old and divided into four groups: young WTR yWTR as the control, aged WTR aWTR, aged TGR aTGR and aged TGRs with HOE140 aTGRH. Erectile function of all rats was evaluated by cavernous nerve electrostimulation method and measured by the ratio of intracavernous pressure- mean arterial pressure ICP-MAP in rats. Expression levels of cAMP and cGMP were assessed, and related signaling pathways were detected by western blot, immunohistochemistry and RT-PCR. Our experiment results showed erectile function of the aWTR group and aTGRH group was lower compared with those of other two groups. Also, expression levels of cAMP and cGMP were significantly lower than those of other two groups. Moreover, expressions of related signaling pathways including DDAH-ADMA-NOS-cGMP and COX-2-PTGIS-cAMP were also downregulated in the corpus cavernosum of rats in aWTR group. Our finding revealed hKLK1 played a protective role in age-related ED. The DDAH-ADMA-NOS-cGMP and COX-2-PTGIS-cAMP pathways that were linked to the mechanism hKLK1 could increase the levels of cGMP and cAMP, which might provide novel therapy targets for age-related ED.



Autor: Kai Cui , Yang Luan , Zhe Tang, Ke Rao, Tao Wang, Zhong Chen, Shaogang Wang, Jihong Liu , Daowen Wang

Fuente: http://plos.srce.hr/



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