A novel angiotensin I-converting enzyme inhibitory peptide APPLRP from Grifola frondosa ameliorated the Ang II-induced vascular modeling in zebrafish model by mediating smooth muscle cells.

Autor: Song T; School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, People's Republic of China; Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, People's Republic of China; National Experimental Teaching Demonstration Center Food Engineering and Quality and Safety, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, People's Republic of China; Food (edible fungus) Processing Technology Research Center of Qing-Yuan, Hangzhou, Zhejiang 310018, People's Republic of China., Zhang T; School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, People's Republic of China; Food (edible fungus) Processing Technology Research Center of Qing-Yuan, Hangzhou, Zhejiang 310018, People's Republic of China., Cai Q; School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, People's Republic of China; Food (edible fungus) Processing Technology Research Center of Qing-Yuan, Hangzhou, Zhejiang 310018, People's Republic of China., Ding YY; School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, People's Republic of China; Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, People's Republic of China; National Experimental Teaching Demonstration Center Food Engineering and Quality and Safety, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, People's Republic of China; Food (edible fungus) Processing Technology Research Center of Qing-Yuan, Hangzhou, Zhejiang 310018, People's Republic of China., Gu Z; School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, People's Republic of China; Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, People's Republic of China; National Experimental Teaching Demonstration Center Food Engineering and Quality and Safety, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, People's Republic of China; Food (edible fungus) Processing Technology Research Center of Qing-Yuan, Hangzhou, Zhejiang 310018, People's Republic of China. Electronic address: guzy84@163.com.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Oct; Vol. 278 (Pt 4), pp. 134998. Date of Electronic Publication: 2024 Aug 22.
DOI: 10.1016/j.ijbiomac.2024.134998
Abstrakt: Grifola frondosa has garnered significant popularity as an edible mushroom attributable to its exceptional taste and nutritional benefits. This study isolated APPLRP, a potent ACE-inhibitory peptide, from the alcohol-soluble fraction of Grifola frondosa. The underlying mechanisms of APPLRP in antihypertension were explored through computational chemistry, cell experiments, and zebrafish model. Results demonstrated that APPLRP was an active competitive ACE inhibitor (IC 50  = 29.93 μM) that could bind to the active pocket S2 and S1' of ACE. APPLRP exhibited resistance to pepsin and pancreatin digestion. In vitro experiments revealed that APPLRP significantly attenuated Ang II-induced VSMCs proliferation and migration by down-regulating AT1R expression and inhibiting ERK1/2 and STAT3 phosphorylation. APPLRP intervention significantly ameliorated myocardial fibrosis, as evidenced by reductions in cardiac output, blood flow velocity, and cardiac collagen deposition levels in Ang II-induced hypertensive zebrafish model. Furthermore, APPLRP improved vascular remodeling in hypertensive zebrafish, indicated by increased vessel diameter and decreased vessel wall thickness. Notably, APPLRP treatment resulted in down-regulation of ACE and up-regulation of ACE2 expression in the vessels of hypertensive zebrafish. These findings indicated that APPLRP was a representative component of Grifola frondosa peptides, and its antihypertensive effects were associated with ACE inhibition and the improvement of VSMCs-mediated vascular remodeling.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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