Kinetic characterization and inhibition of the rat MAB elastase-2, an angiotensin I-converting serine protease

Canadian Journal of Physiology and Pharmacology
Carlos Ferreira SantosEduardo B Oliveira

Abstract

An elastase-2 has been recently described as the major angiotensin (Ang) II-forming enzyme of the rat mesenteric arterial bed (MAB) perfusate. Here, we have investigated the interaction of affinity-purified rat MAB elastase-2 with some substrates and inhibitors of both pancreatic elastases-2 and Ang II-forming chymases. The Ang II precursor [Pro 11 -D-Ala 12]-Ang I was converted into Ang II by the rat MAB elastase-2 with catalytic efficiency of 8.6 min-1 microM-1, and the chromogenic substrates N-succinyl-Ala-Ala-Pro-Leu-p-nitroanilide and N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide were hydrolyzed by the enzyme with catalytic efficiencies of 10.6 min-1 microM-1 and 7.6 min-1 microM-1, respectively. The non-cleavable peptide inhibitor CH-5450 inhibited the rat MAB elastase-2 activities toward the substrates Ang I (IC50 = 49 microM) and N-succinly-Ala-Ala-Pro-Phe-p-nitroanilide (IC 50 = 4.8 microM), whereas N-acetyl-Ala-Ala-Pro-Leu-chloromethylketone, an effective active site-directed inhibitor of pancreatic elastase-2, efficiently blocked the Ang II-generating activity of the rat MAB enzyme (IC 50 = 4.5 microM). Altogether, the data presented here confirm and extend the enzymological similarities between pancreatic elastase-2 and...Continue Reading

References

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Citations

Mar 28, 2007·BMC Biotechnology·Jun LiaoJeremy Minshull
Feb 21, 2009·Journal of Periodontology·C F SantosM C O Salgado
Aug 6, 2015·PloS One·Carlos F SantosAndrew S Greene
Oct 1, 2011·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·C BecariM C O Salgado
Jan 13, 2005·Canadian Journal of Physiology and Pharmacology·Carlos F SantosEduardo B Oliveira
Jun 12, 2009·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Hugo Juarez Vieira PereiraEduardo Brandt Oliveira
Sep 15, 2005·Journal of Cardiovascular Pharmacology·Christiane BecariMaria Cristina O Salgado
Apr 26, 2003·American Journal of Physiology. Heart and Circulatory Physiology·Carlos F SantosAndrew S Greene
May 24, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Christiane BecariMaria Cristina O Salgado

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