Protective Effect of Peptide Calcium Channel Blocker Omega-Hexatoxin-Hv1a on Epithelial Cell during Ischemia–Reperfusion Injury

Author:

Iurova Elena1,Rastorgueva Eugenia12ORCID,Beloborodov Evgenii1,Pogodina Evgeniya1,Fomin Aleksandr1,Sugak Dmitrii1,Viktorov Denis1,Tumozov Ivan1,Saenko Yury1

Affiliation:

1. Laboratory of Research and Development of Peptide Drugs and Vaccines, S. P. Kapitsa Technological Research Institute, Ulyanovsk State University, 432017 Ulyanovsk, Russia

2. Department of General and Clinical Pharmacology and Microbiology, Faculty of Medicine, Ulyanovsk State University, 432017 Ulyanovsk, Russia

Abstract

Ischemia–reperfusion injury (IRI) is a common phenomenon that develops both from natural causes and during major operations. Many intracellular processes mediated by calcium ions are involved in the development of IRI. Currently, chemical calcium channel blockers are used but they have a number of limitations. In this article, we study the effect of the omega-hexatoxin-Hv1a peptide toxin, an alternative to chemical calcium channel blockers, on the mechanisms of IRI development in epithelial cell culture. The toxin was produced using solid phase peptide synthesis. IRI was caused by deprivation of glucose, serum and oxygen. The data obtained demonstrate that the omega-hexatoxin-Hv1a toxin in nanomolar concentrations is able to prevent the development of apoptosis and necrosis in epithelial cells by reducing the concentration of calcium, sodium and potassium ions, as well as by delaying rapid normalization of the pH level, affecting the mitochondrial potential and oxidative stress. This toxin can be used as an alternative to chemical calcium channel blockers for preventing tissue and organ IRI due to its low-dose requirement and high bioavailability.

Funder

Ministry of Science and Higher Education of the Russian Federation

Publisher

MDPI AG

Subject

Drug Discovery,Pharmaceutical Science,Molecular Medicine

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