Peptide toxins targeting ion channels as cytoprotective agents in ischemia-reperfusion injury of epithelial cells

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Abstract
Ischemia-reperfusion injury (IRI) is a complex process accompanying cessation of blood supply to an organ or tissue followed by subsequent restoration of blood circulation. The IRI is especially prominent in surgery and organ transplantation. One of the strategies for reducing organ and tissue damage during transplantation is regulation of intracellular ion concentrations. Maintenance of ion concentrations in the cell during damage development can be controlled by influencing voltage-dependent ion channels with certain types of compounds. We propose the peptide toxins tropic to calcium (omega-hexatoxin-Hv1a) and sodium (mu-agatoxin-Aa1a) voltage-dependent ion channels as potential agents reducing IRI. The toxins were obtained using solid-phase peptide synthesis. The IRI modeling for evaluation of the action of toxins was carried out on a culture of epithelial cells CHO-K1 during their incubation under conditions of hypoxia and nutrient deprivation followed by subsequent replenishment of the nutrient medium. The level of cell death, concentrations of calcium, sodium, potassium ions, and pH were recorded using a multimodal plate reader and fluorescent dyes. Experiments have shown that regardless of different mechanisms of action, both toxins reduced the development of CHO-K1 cell death by changing ion concentrations and maintaining the pH level.

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