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Chymase inhibitor-s...
Chymase inhibitor-sensitive synthesis of endothelin-1 (1-31) by recombinant mouse mast cell protease 4 and human chymase
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Semaan, Walid (author)
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Desbiens, Louisane (author)
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Houde, Martin (author)
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Labonte, Julie (author)
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Gagnon, Hugo (author)
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Yamamoto, Daisuke (author)
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Takai, Shinji (author)
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Laidlaw, Tanya (author)
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Bkaily, Ghassan (author)
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Schwertani, Fadel (author)
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- Pejler, Gunnar (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB)
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Levesque, Christine (author)
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Desjardins, Roxane (author)
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Day, Robert (author)
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D'Orleans-Juste, Pedro (author)
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(creator_code:org_t)
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- Elsevier BV, 2015
- 2015
- English.
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In: Biochemical Pharmacology. - : Elsevier BV. - 0006-2952 .- 1356-1839 .- 1873-2968. ; 94:2, s. 91-100
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://res.slu.se/i...
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Abstract
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- Important structural differences imply that human and mouse mast cell chymases may differ with respect to their enzymatic properties. We compared in this study the catalytic efficiencies of recombinant human chymase (rCMA1) and its functional murine homologue recombinant mouse mast cell protease-4 (rmMCP-4) toward a fluorogenic chymase substrate (Suc-Ala-Ala-Pro-Phe-7-amino-4-methylcoumarin (AMC) and by their ability to convert Big-endothelin (ET)-1 into ET-1 (1-31) using a LC/MS/MS system. Activities toward a fluorogenic substrate (Suc-Leu-Leu-Val-Tyr-AMC) and Big ET-1 were also measured in extracts from mouse peritoneal mast cells, LUVA human mast cell-like cells and human aortas. The specificity of these activities was assessed with the chymase inhibitor TY-51469 (2-[4-(5-fluoro-3-methylbenzo[b]thiophen-2-yl)sulfonamido-3-methanesulfonyl-phenyl]thiazole-4-carboxylic acid). For similar affinities, rmMCP-4 showed a higher activity toward the fluorogenic substrate and a higher ability to process Big ET-1 as compared to recombinant CMA1 (chymase activity (k(cat)/K-M in mu M-1 s(-1)): 2.29 x 10(-4) vs. 6.41 x 10(-6); ET-1 (1-31) production: 2.19 x 10(-3) vs. 6.57 x 10(-5)), and both of these activities of mouse and human chymase were sensitive to TY-51469. Furthermore, extracts from mouse peritoneal mast cells, LUVA cells and human aorta homogenates contained processing activities toward the fluorogenic chymase substrate as well as Big ET-1, all of which were sensitive to TY-51469. Finally, the pressor responses to Big ET-1 but not to ET-1 were significantly reduced in conscious and free moving mMCP-4 KO mice when compared to wild type congeners. Our results suggest that both mouse and human chymases have potent ET-1 (1-31)-producing abilities, with the murine isoform being more efficient.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
Keyword
- Chymase
- Recombinant enzymes
- Mass spectrometry
- Radiotelemetry
- In silico analysis
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Semaan, Walid
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Desbiens, Louisa ...
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Houde, Martin
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Labonte, Julie
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Gagnon, Hugo
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Yamamoto, Daisuk ...
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show more...
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Takai, Shinji
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Laidlaw, Tanya
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Bkaily, Ghassan
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Schwertani, Fade ...
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Pejler, Gunnar
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Levesque, Christ ...
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Desjardins, Roxa ...
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Day, Robert
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D'Orleans-Juste, ...
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show less...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Pharmacology and ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Pharmaceutical S ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Immunology
- Articles in the publication
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Biochemical Phar ...
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Uppsala University
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Swedish University of Agricultural Sciences