Effect of mu-agatoxin-Aa1a peptide toxin on the expression of genes regulating ischemia- reperfusion cell injury

The search for diagnostic tests assessing the cardiovascular disease risk is a major focus in medicine. Genetic factors together with external influence and concomitant diseases contribute to ischemic damage. Despite the active use of targeted therapy drugs, little data has been obtained on their negative impact. To solve the problem, it is proposed to use arthropod peptide toxins that have selectivity for ion channels, chemical, thermal and biological stability, and resistance to proteases. Objective: The aim of the paper is to study the effect of mu-agatoxin-Aa1a toxin on the expression profile of Scn5a, Scn4a, Cacna1c, Plce1, Elavl1, Senp, Parp1, Xiap and Orail1 genes under ischemia-reperfusion injury model. Materials and methods. H9C2 cell culture was used. The ischemia-reperfusion injury model was reproduced by incubating the cells in a low-glucose, serum and oxygen (18 h) medium, and subsequent incubation in a complete nutrient medium (2 h). The toxin was introduced at the initial stage of reperfusion. Solid-phase peptide synthesis was used for this purpose. Real-time PCR was used to measure the amount of gene expression. The primer sequence was selected in the NCBI nucleotide sequence database. Statistical processing was conducted using OriginPro 2018. Results: The mu-agatoxin-Aa1a toxin at a concentration of 50 nM in the H9C2 cell culture under ischemia-reperfusion injury contributed to the suppression of Scn4a, Cacna1c, Plce1, Orail1 and Scn5a gene expression and the enhancement of Elavl1 and Xiap gene expression. Conclusion. The obtained results provide new insights into the intracellular molecular mechanisms induced by ischemia-reperfusion injury. The mu-agatoxin-Aa1a toxin, which affects the modulation of Scn5a, Scn4a, Cacna1c, Plce1, Elavl1, Senp, Parp1, Xiap and Orail1 gene expression, can be used for targeted regulation of the main elements of the pathological reaction.