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Involvement of DDAH/ADMA/NOS/cGMP and COX-2/PTGIS/cAMP Pathways in Human Tissue Kallikrein 1 Protecting Erectile Function in Aged Rats.

التفاصيل البيبلوغرافية
العنوان: Involvement of DDAH/ADMA/NOS/cGMP and COX-2/PTGIS/cAMP Pathways in Human Tissue Kallikrein 1 Protecting Erectile Function in Aged Rats.
المؤلفون: Cui K; Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and technology, Wuhan, Hubei, China.; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Luan Y; Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and technology, Wuhan, Hubei, China.; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Tang Z; Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and technology, Wuhan, Hubei, China.; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Rao K; Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and technology, Wuhan, Hubei, China.; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Wang T; Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and technology, Wuhan, Hubei, China.; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Chen Z; Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and technology, Wuhan, Hubei, China.; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Wang S; Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and technology, Wuhan, Hubei, China.; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Liu J; Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and technology, Wuhan, Hubei, China.; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Wang D; Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
المصدر: PloS one [PLoS One] 2017 Jan 19; Vol. 12 (1), pp. e0170427. Date of Electronic Publication: 2017 Jan 19 (Print Publication: 2017).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Aging/*physiology , Penile Erection/*physiology , Tissue Kallikreins/*physiology, Aging/genetics ; Amidohydrolases/metabolism ; Animals ; Arginine/analogs & derivatives ; Arginine/metabolism ; Cyclic AMP/metabolism ; Cyclic GMP/metabolism ; Cyclooxygenase 2/genetics ; Cyclooxygenase 2/metabolism ; Cytochrome P-450 Enzyme System/genetics ; Cytochrome P-450 Enzyme System/metabolism ; Erectile Dysfunction/genetics ; Erectile Dysfunction/metabolism ; Erectile Dysfunction/physiopathology ; Humans ; Intramolecular Oxidoreductases/genetics ; Intramolecular Oxidoreductases/metabolism ; Male ; Nitric Oxide Synthase Type I/genetics ; Nitric Oxide Synthase Type I/metabolism ; Nitric Oxide Synthase Type III/genetics ; Nitric Oxide Synthase Type III/metabolism ; Penile Erection/genetics ; Penis/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley ; Rats, Transgenic ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Signal Transduction ; Tissue Kallikreins/genetics
مستخلص: 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.
Competing Interests: The authors have declared that no competing interests exist.
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المشرفين على المادة: 0 (RNA, Messenger)
0 (Recombinant Proteins)
63CV1GEK3Y (N,N-dimethylarginine)
9035-51-2 (Cytochrome P-450 Enzyme System)
94ZLA3W45F (Arginine)
E0399OZS9N (Cyclic AMP)
EC 1.14.13.39 (Nitric Oxide Synthase Type I)
EC 1.14.13.39 (Nitric Oxide Synthase Type III)
EC 1.14.13.39 (Nos1 protein, mouse)
EC 1.14.13.39 (Nos3 protein, mouse)
EC 1.14.99.1 (Cyclooxygenase 2)
EC 1.14.99.1 (Ptgs2 protein, rat)
EC 3.4.21.35 (Tissue Kallikreins)
EC 3.5.- (Amidohydrolases)
EC 3.5.3.18 (dimethylargininase)
EC 5.3.- (Intramolecular Oxidoreductases)
EC 5.3.99.4 (prostacyclin synthetase)
H2D2X058MU (Cyclic GMP)
تواريخ الأحداث: Date Created: 20170120 Date Completed: 20170814 Latest Revision: 20181113
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC5245815
DOI: 10.1371/journal.pone.0170427
PMID: 28103290
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0170427