Human Tissue Kallikrein 1 Improves Erectile Dysfunction of Streptozotocin-Induced Diabetic Rats by Inhibition of Excessive Oxidative Stress and Activation of the PI3KAKTeNOS Pathway
Joint Authors
Liu, Jihong
Wang, Shaogang
Luan, Yang
Cui, Kai
Tang, Zhe
Ruan, Yajun
Liu, Kang
Wang, Tao
Chen, Zhong
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-18, 18 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-02-29
Country of Publication
Egypt
No. of Pages
18
Main Subjects
Abstract EN
Objective.
To investigate the protective effects and mechanisms of human tissue kallikrein 1 (hKLK1) on type 1 diabetes mellitus- (DM-) induced erectile dysfunction in rats.
Materials and Methods.
The homozygous transgenic rats (TGR) harboring the hKLK1 gene and age-matched wild-type Sprague Dawley rats (WTR) were involved, and intraperitoneal injection of streptozotocin was utilized to induce diabetes in rats.
Forty-eight-week-old male rats were randomly divided into a WTR group, TGR group, diabetic WTR group (WTDM), diabetic TGR group (TGDM), and TGDM with HOE140 group (TGDMH), with eight rats in each group.
Twelve weeks later, the erectile response of all rats was detected by cavernous nerve electric stimulation, and corpus cavernosums were harvested to evaluate the levels of cavernous oxidative stress (OS), apoptosis, fibrosis, and involved pathways.
Moreover, cavernous smooth muscle cells (CSMC) and endothelial cells (EC) were primarily isolated to build a coculture system for a series of in vitro verification.
Results.
The hKLK1 gene only existed and was expressed in TGR.
Compared to the WTR group, the WTDM group showed a lower erectile response, overactivated OS and apoptosis, inhibited PI3K/AKT/eNOS pathway, and aggravated cavernous fibrosis.
However, hKLK1 in the TGDM group could improve these pathological changes induced by DM, while its protective effects could be weakened by HOE140 in the TGDMH group.
In the coculture system, hKLK1 could induce CSMC relaxation through activating PI3K/eNOS/cGMP signaling and inhibiting calcium ion influx under physiological condition.
It could also resist the increased reactive oxygen species, apoptosis level, and reduced cGMP level in CSMC under high-glucose condition.
Conclusions.
hKLK1 preserves erectile function of DM rats through its antitissue excessive OS, apoptosis, and fibrosis effects, as well as activation of the PI3K/AKT/eNOS/cGMP pathway in the penis.
Moreover, hKLK1 promotes relaxation and prevents high glucose-induced injuries of CSMC mediated by EC-CSMC crosstalk.
American Psychological Association (APA)
Luan, Yang& Cui, Kai& Tang, Zhe& Ruan, Yajun& Liu, Kang& Wang, Tao…[et al.]. 2020. Human Tissue Kallikrein 1 Improves Erectile Dysfunction of Streptozotocin-Induced Diabetic Rats by Inhibition of Excessive Oxidative Stress and Activation of the PI3KAKTeNOS Pathway. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-18.
https://search.emarefa.net/detail/BIM-1205222
Modern Language Association (MLA)
Luan, Yang…[et al.]. Human Tissue Kallikrein 1 Improves Erectile Dysfunction of Streptozotocin-Induced Diabetic Rats by Inhibition of Excessive Oxidative Stress and Activation of the PI3KAKTeNOS Pathway. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-18.
https://search.emarefa.net/detail/BIM-1205222
American Medical Association (AMA)
Luan, Yang& Cui, Kai& Tang, Zhe& Ruan, Yajun& Liu, Kang& Wang, Tao…[et al.]. Human Tissue Kallikrein 1 Improves Erectile Dysfunction of Streptozotocin-Induced Diabetic Rats by Inhibition of Excessive Oxidative Stress and Activation of the PI3KAKTeNOS Pathway. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-18.
https://search.emarefa.net/detail/BIM-1205222
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1205222