Content of apoptosis factors and self-organization processes in the mitochondria of heart cells in female mice C57BL/6 under growth of melanoma B16 / F10 linked with comorbid pathology
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The aim is to study some mechanisms of regulation of apoptosis and self-organization in the mitochondria in the heart cells in female mice during the growth of experimental melanoma B16/F10 linked with chronic neurogenic pain as comorbid pathology.
Materials and methods
The work has been performed in female mice of the C57BL/6 strain (n=168).The following experimental groups have been presented: the group of intact mice (n=21), the control group (n=21) to reproduce chronic neurogenic pain (CNP), the comparison group (n=63) with a standard growth of melanoma B16/F10 and the main group (n=63) with CNP + melanoma B16 / F10. In mitochondria the following concentrations have been determined by the ELISA method: cytochrome C (ng/mg protein), caspase-9 (ng/mg protein), Bcl-2 (ng/mg protein), AIF (ng/mg protein) and calcium (mmol/g protein). The Statistica 10.0 software was used for statistical analysis.
As against the intact values, the standard growth of melanoma reduced in the mitochondria of the heart cells the level of calcium in week 1-2 by 2.9 and 6.7 times, respectively, the AIF content in week 2-3 by 1.4 times (p < 0.05) and 2 times, respectively; Вcl-2 after 1-2 weeks by 1.7 and 2.9 times, while cytochrome C and caspase 9 remained stable throughout the entire period of the melanoma growth. CNP induced a decrease in the level of Ca2+ by 3.2 times, that in Bcl-2 by 1.3 times (p<0.05), in caspase 9 by 1.5 times and an increase in the AIF content by 2.3 times compared with the intact values. After 1 week of the melanoma growth against the background of CNP, the levels of Ca2+ and caspase 9 increased by 5.3 times and 2.4 times relative to the control values, in the subsequent periods of the melanoma growth, Ca2+ decreased almost to undetectable values. AIF, Bcl-2, and cytochrome C changed abruptly, but by the end of the experiment they were at a low level with a 5.2-fold decrease in AIF, and a 2.2-fold decrease in Bcl-2 and cytochrome C content.
The standard growth of B16/F10 melanoma in female mice is accompanied by a decline in the respiratory and energy function of the heart cell mitochondria. The growth of melanoma, stimulated by CNP as comorbid pathology, exacerbates the mitochondrial dysfunction, suppresses the activity of apoptosis factors and leads to the development of myocardial infarction in the vast majority of animals, accompanied by compensatory mitochondrial aggregation and chemiluminescence.
Elena M. Frantsiyants, Irina V. Neskubina, Alla I. Shikhlyarova, Marina A. Yengibaryan, Larisa N. Vashchenko, Ekaterina I. Surikova, Lyudmila A. Nemashkalova, Irina V. Kaplieva, Lidia K. Trepitaki, Valeria А. Bandovkina, Yulia А. Pogorelova. Content of apoptosis factors and self-organization processes in the mitochondria of heart cells in female mice C57BL/6 under growth of melanoma B16 / F10 linked with comorbid pathology. Cardiometry; Issue 18; May 2021; p.121-130; DOI: 10.18137/cardiometry.2021.18.121130; Available from: http://www.cardiometry.net/issues/no18-may-2021/apoptosis-factors