دورية أكاديمية
أعرض في EDS

3-Hydroxy-3-methylglutaryl-CoA synthase 2 facilitates erectile dysfunction via inhibiting autophagy by enhancing the mammalian target of rapamycin pathway in type 1 diabetic mellitus rats.

التفاصيل البيبلوغرافية
العنوان: 3-Hydroxy-3-methylglutaryl-CoA synthase 2 facilitates erectile dysfunction via inhibiting autophagy by enhancing the mammalian target of rapamycin pathway in type 1 diabetic mellitus rats.
المؤلفون: Dai Z; Department of Urology, China and Sichuan Provincial Clinical Research Center for Kidney Diseases, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China., Zeng Y; Department of Urology, China and Sichuan Provincial Clinical Research Center for Kidney Diseases, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China., Tan X; Department of Urology, China and Sichuan Provincial Clinical Research Center for Kidney Diseases, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China., Zhou T; Department of Urology, China and Sichuan Provincial Clinical Research Center for Kidney Diseases, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China., Li X; Department of Urology, China and Sichuan Provincial Clinical Research Center for Kidney Diseases, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China., Deng Q; Department of Urology, China and Sichuan Provincial Clinical Research Center for Kidney Diseases, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China.
المصدر: Andrology [Andrology] 2024 Sep; Vol. 12 (6), pp. 1449-1462. Date of Electronic Publication: 2024 Jan 25.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101585129 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2047-2927 (Electronic) Linking ISSN: 20472919 NLM ISO Abbreviation: Andrology Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Oxford : Wiley-Blackwell, 2013-
مواضيع طبية MeSH: Erectile Dysfunction*/metabolism , Erectile Dysfunction*/physiopathology , Autophagy* , TOR Serine-Threonine Kinases*/metabolism , Diabetes Mellitus, Type 1*/metabolism , Diabetes Mellitus, Type 1*/complications , Diabetes Mellitus, Experimental*/metabolism , Diabetes Mellitus, Experimental*/complications , Signal Transduction* , Rats, Sprague-Dawley* , Hydroxymethylglutaryl-CoA Synthase*/metabolism , Hydroxymethylglutaryl-CoA Synthase*/genetics, Animals ; Male ; Rats ; Penis/metabolism ; Endothelial Cells/metabolism ; Nitric Oxide Synthase Type III/metabolism
مستخلص: Background: The relationship between erectile dysfunction (ED) and type 1 diabetes mellitus (T1DM) is currently a hot topic of medical research. It has been reported that autophagy plays a crucial role in causing erectile dysfunction in T1DM. Recent research has shown that mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) is strongly linked to the development of T1DM. However, the specific mechanism by which it regulates the erectile function is not yet fully understood.
Objectives: To investigate whether HMGCS2 affects erectile function in type 1 diabetic rats by regulating autophagy in corpus cavernosum endothelial cells (CCECs).
Materials and Methods: First, the rat model of T1DM was established. Then, the ratio of maximum penile intracavernous pressure (ICPmax) and mean arterial pressure (MAP) was detected to assess the erectile function in various groups, and the protein expression of HMGCS2, mTOR and p-mTOR was evaluated by western blot (WB) and immunohistochemistry (IHC). To explore the relationship between HMGCS2 and the mTOR signaling pathway in T1DM ED rats, we silenced the expression of HMGCS2 and activated the mTOR signaling pathway with MHY1485 in CCECs and then assessed the expression of beclin1, P62, LC3, autophagosome, endothelial nitric oxide synthase (eNOS), phosphorylation of eNOS (p-eNOS), and nitric oxide (NO) to evaluate autophagy and the erectile function by reverse transcription quantitative polymerase chain reaction and western blot.
Results: The study conducted on T1DM ED rats showed that the expression of HMGCS2 was significantly increased, while the autophagy was suppressed. Additionally, the mTOR signaling pathway was highly activated. In contrast, when HMGCS2 was silenced in vitro, p-mTOR/mTOR was reduced, and autophagy was improved. These effects were accompanied by the enhanced activity of eNOS. Furthermore, when HMGCS2 was silenced and the mTOR signaling pathway was simultaneously activated, the results revealed a decrease in autophagy as well as a reduction in activity of eNOS in comparison to just silencing HMGCS2 alone.
Discussion and Conclusion: HMGCS2 upregulation in T1DM rats inhibited autophagy and eNOS activity by activating the mTOR pathway and led to a decrease in the erectile function.
(© 2024 American Society of Andrology and European Academy of Andrology.)
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معلومات مُعتمدة: 19078 Affiliated Hospital of Southwest Medical University; 16024 Affiliated Hospital of Southwest Medical University; 2019YFS0537-6 Sichuan Provincial Clinical Research Center for Kidney Diseases; 15197 Luzhou Science and Technology Bureau; 2022-JYJ-115 Luzhou Science and Technology Bureau; 00031000 Southwest Medical University; 82303853 National Natural Science Foundation of China
فهرسة مساهمة: Keywords: HMGCS2; autophagy; erectile dysfunction; mTOR; type 1 diabetic mellitus
المشرفين على المادة: EC 2.7.11.1 (TOR Serine-Threonine Kinases)
EC 2.7.1.1 (mTOR protein, rat)
EC 2.3.3.10 (Hydroxymethylglutaryl-CoA Synthase)
EC 1.14.13.39 (Nitric Oxide Synthase Type III)
تواريخ الأحداث: Date Created: 20240126 Date Completed: 20240814 Latest Revision: 20240814
رمز التحديث: 20240814
DOI: 10.1111/andr.13600
PMID: 38273709
قاعدة البيانات: MEDLINE
الوصف
تدمد:2047-2927
DOI:10.1111/andr.13600