In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e21560-e21560
Abstract:
e21560 Background: Mitochondrial dysfunction is has a significant impact on the development of heart disease and is a characteristic feature of the heart physiopathology. Our purpose was to analyze some mechanisms of apoptosis regulation and self-organization in the mitochondria of the heart cells in mice with melanoma growing in presence of chronic neurogenic pain (CNP). Methods: The study included female C57BL/6 mice (n = 105) divided into groups: intact animals (n = 21); controls (C, n = 21) with a CNP model created by bilateral sciatic nerve ligation under xylazine/zoletil anesthesia; main group (CNP+B16/F10, n = 63) with B16/F10 melanoma transplanted after CNP creation. After decapitation, mitochondria of the heart were isolated by differential centrifugation. Levels of cytochrome C (ng/mg of protein), caspase 9 (ng/mg of protein), Bcl-2 (ng/mg of protein), AIF (ng/mg of protein), Ca 2+ (mmol/g of protein) were determined in mitochondrial samples by ELISA. Results: CNP downregulated levels of Ca 2+ by 3.2 times, Bcl-2 by 1.3 times (p 〈 0.05) and caspase 9 by 1.5 times (p 〈 0.05), compared to intact mice. AIF levels, on the contrary, were elevated by 2.3 times, and cytochrome C did not differed statistically significantly from intact values. After a week of B16/F10 growth in presence of CNP, levels of Ca 2+ in the mitochondria of the heart increased by 5.3 times relative to C values. Further on, Ca 2+ decreased to almost undetectable values. The AIF levels changed abruptly: after 1 week it increased by 3.7 times, after 2 weeks it declined to C levels, and after 3 weeks it became 5.2 times lower than in C and 2.3 times lower than in intact animals. Bcl-2 and cytochrome C changed similarly: Bcl-2 after 1 week of melanoma growth in presence of CNP increased 1.7 times (p 〈 0.05) compared to C, and then after 2-3 weeks it declined and became on average 2.2 times lower than in the mitochondria of the C group; levels of cytochrome C after 1 week did not differed significantly from the values in C, and after 2-3 weeks they decreased by 2.2 times. The levels of caspase 9 in CNP+B16/F10 were on average 2.4 times higher than C values throughout the study. The cold light of high brightness - chemiluminescence was recorded in samples of mitochondrial suspension after 2-3 weeks of CNP+B16/F10. The glow in heart mitochondrial samples was accompanied by bright flashes and a 10-15 second intense white glow with a gradual fading and settling of a large filamentous aggregation of mitochondria on the substrate layer. CNP contributed to the energy supply system blocking in the energy systems of cardiomyocytes. Conclusions: Mitochondrial mechanisms of apoptosis and self-organization of subcellular energy structures in the conditions of malignant tumor growth in presence of CNP are mediated by disruption of polyenzymatic apoptosis regulation systems, and a high level of oxidative stress that induces chemiluminescence of cardiomyocyte mitochondrial associates.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2022.40.16_suppl.e21560
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2022
detail.hit.zdb_id:
2005181-5
