MP86-12 HUMAN TISSUE KALLIKREIN 1 RESTORES ERECTILE FUNCTION OF STREPTOZOTOCIN- INDUCED DIABETIC RATS BY ACTIVATING PI3K/ENOS PATHWAY, INHIBITING OXIDATIVE STRESS AND APOPTOSIS IN THE CORPUS CAVERNOSUM

Abstract

You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology I1 Apr 2016MP86-12 HUMAN TISSUE KALLIKREIN 1 RESTORES ERECTILE FUNCTION OF STREPTOZOTOCIN- INDUCED DIABETIC RATS BY ACTIVATING PI3K/ENOS PATHWAY, INHIBITING OXIDATIVE STRESS AND APOPTOSIS IN THE CORPUS CAVERNOSUM Yang Luan, Yajun Ruan, Tao Wang, Yan Zhang, Kai Cui, Rui Li, Jun Yang, Ruibao Chen, Shaogang Wang, Jihong Liu, and Zhangqun Ye Yang LuanYang Luan More articles by this author , Yajun RuanYajun Ruan More articles by this author , Tao WangTao Wang More articles by this author , Yan ZhangYan Zhang More articles by this author , Kai CuiKai Cui More articles by this author , Rui LiRui Li More articles by this author , Jun YangJun Yang More articles by this author , Ruibao ChenRuibao Chen More articles by this author , Shaogang WangShaogang Wang More articles by this author , Jihong LiuJihong Liu More articles by this author , and Zhangqun YeZhangqun Ye More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2320AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Our previous study has proved the protective role of human tissue kallikrein 1 (hKLK1) in erectile function of aged rats with the transgenic Sprague-Dawley (SD) rats harboring hKLK1 gene (TGR), but its effect on diabetic erectile dysfunction (ED) is still unknown. METHODS Eight-week-old male wild type SD rats (WTR) and age matched TGR were randomly divided into five groups: citrate buffer treated (1) WTR and (2) TGR; streptozotocin-induced (3) diabetic wild type rats (WTDM) and (4) diabetic transgenic rats (TGDM); (5) TGDM with daily administration of bradykinin receptor 2 inhibitor HOE 140 (TGDMH). Erectile response was measured by cavernous nerve electrostimulation after 12-week treatment. Then the corpus cavernosum (CC) tissues were harvested for hKLK1 gene identification and mechanism exploration. The regulation of hKLK1 on PI 3 kinase (PI3K)/ endothelial nitric oxide synthase (eNOS) pathway was detected within CC in vivo and TGR derived cavernous smooth muscle cell (CSMC) in vitro. In addition, the effect of hKLK1 on oxidative stress and apoptosis in CC of diabetic rats and high glucose treated CSMC was also evaluated. RESULTS hKLK1 attenuated the decreased erectile function of WTDM, while the protective effect was abolished in TGDMH. The decrease of PI3K(p55), AKT, eNOS, phospho-eNOS(Ser1177), cyclic guanosine monophosphate (cGMP) and increase of phospho-eNOS(Thr495), phosphodiesterase type 5, L-type calcium channel in CC of WTDM were improved in that of TGDM, but deteriorated again by HOE 140. Meanwhile, hKLK1 could elevate the level of cGMP and reduce the concentration of Ca2+ in CSMC in vitro, but these changes were diminished by B2R, PI3K or eNOS inhibitors. In addition, the CC of WTDM had higher proteins expression of nicotinamide adenine dinucleotide phosphate oxidase, malondialdehyde level, lower activity of superoxide dismutase and elevated apoptosis percentage when compared to WTR. However, hKLK1 improved these parameters in TGDM and inhibition with HOE 140 would abolish these advantages. Besides, the level of reactive oxygen species (ROS) and apoptosis rate elevated in high glucose treated CSMC in a concentration-dependent manner and hKLK1 could considerably inhibit the generation of ROS and cell apoptosis in vitro. CONCLUSIONS These results indicate that hKLK1 could restore diabetic ED through activation of PI3K/eNOS signaling and inhibition of oxidative stress and apoptosis in CC. © 2016FiguresReferencesRelatedDetailsCited bySeftel A (2016) Re: Preserved Erectile Function in the Aged Transgenic Rat Harboring Human Tissue Kallikrein 1Journal of Urology, VOL. 197, NO. 2, (493-493), Online publication date: 1-Feb-2017. Volume 195Issue 4SApril 2016Page: e1110 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Yang Luan More articles by this author Yajun Ruan More articles by this author Tao Wang More articles by this author Yan Zhang More articles by this author Kai Cui More articles by this author Rui Li More articles by this author Jun Yang More articles by this author Ruibao Chen More articles by this author Shaogang Wang More articles by this author Jihong Liu More articles by this author Zhangqun Ye More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...