Caveolae Depletion Contributes to Vasorelaxant Effects of Chenodeoxycholic Acid
| Autor: | Jin Ma, Yue Cai, Zhongchao Wang, Jin-Wen Yu, Jun-Xiang Bao, Qiang Lv, Yao-Ping Cheng, Huan Liu, Yue Wu, Yu-Ting Su, Yun-Gang Bai |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Nitric Oxide Synthase Type III Physiology Vasodilator Agents Vasodilation Cholic Acid Caveolae Chenodeoxycholic Acid Nitric Oxide lcsh:Physiology Nitric oxide lcsh:Biochemistry Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Enos Internal medicine Chenodeoxycholic acid medicine Animals lcsh:QD415-436 Aorta lcsh:QP1-981 biology Cholesterol Cholic acid Vasorelaxant effect biology.organism_classification Methyl-β-cyclodextrin 030104 developmental biology Endocrinology chemistry Biochemistry Vasoconstriction 030220 oncology & carcinogenesis Endothelial nitric oxide synthase Endothelium Vascular medicine.symptom |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 42, Iss 3, Pp 1013-1024 (2017) |
| ISSN: | 1421-9778 1015-8987 |
| DOI: | 10.1159/000478683 |
| Popis: | Background/Aims: High concentration of bile acids (BAs) induces hydrophobicity-dependent vasorelaxtant effects with hydrophobic BAs showing greater responses than hydrophilic BAs, of which the underlying mechanisms are still unclear. Caveolae are invaginations on membranes of endothelial cells (ECs) entraping endothelial nitric oxide synthase (eNOS) to prevent its activation, which plays a critical role in regulation of vascular function. The purpose of the present study was to investigate the role of caveolae in vasorelaxant effects of BAs. Methods: Chenodeoxycholic acid (CDCA) and cholic acid (CA) were used to represent hydrophobic and hydrophilic BA, respectively. Vascular responses of abdominal aorta were measured by isometric force recording. Morphology of caveolae was examined by transmission electron microscopy. Protein expression of total eNOS (t-eNOS) or phosphorylated eNOS (p-eNOS) was determined by Western blot. Nitric oxide (NO) content was observed by fluorometric assay. Results: We demonstrated that CDCA as well as Methyl-β-cyclodextrin (MCD), a commonly used reagent for cholesterol depletion, reduced potassium chloride (KCl)- or phenylephrine (PE)-elicited vasoconstriction (P < 0.05), and enhanced acetylcholine (Ach)-elicited vasodilatation (P < 0.05) in endothelium-intact abdominal aorta but not in endothelium-denuded or CA-treated vessels. CDCA and MCD, but not CA significantly disrupted caveolae structure on ECs of abdominal aorta which was recovered by cholesterol incubation (P < 0.05). Protein expression of t-eNOS was significantly decreased (P < 0.05), and that of p-eNOS together with NO content was significantly increased in CDCA- and MCD- but not CA-treated vessels (P < 0.05) as compared with vehicle. The effect was reversed by either endothelium-denudation or cholesterol replenishment. Moreover, with cholesterol incubation, no significant differences were found in vascular responses among CDCA-, CA- or vehicle-treated vessels. Conclusion: These results indicate that CDCA diminishes caveolae on ECs of abdominal aorta promoting eNOS phosphorylation and NO production which contributes to its vasorelaxtant effect. |
| Databáze: | OpenAIRE |
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