Abstract
Tumor necrosis factor (TNF) participates in regulation of many processes, including carcinogenesis and apoptosis. However, at present, there are practically no studies on peculiarities of apoptosis control in tnf-knockout (tnf-/-) mice. These mice develop without morphologic abnormalities, but they seem to have impairment of many biological processes, such as inflammation, programmed cell death, etc. Therefore, the goal of our work was to study possible pathways of regulation of apoptosis in the absence of TNF in neurosecretory cells (NSC) of young and old mice. For this purpose, we determined immunohistochemically expression of apoptosis markers caspase-8, caspase-9, Bax, Bcl-2, Mcl-1, neuropeptide vasopressin and the apoptosis level in hypothalamus of tnf-knockout mice of different ages as compared with mice with unchanged level of TNF synthesis. It was shown that the apoptosis activation observed during aging did not depend on the tnf gene and that apoptosis at aging was caspase-dependent. It was revealed that at aging in mouse NSC the external cell death pathway with participation of caspase-8 is activated. The pathways mediating cell death in different neurosecretory centers at aging are different. Thus, in supraoptic nucleus (SON), in all studied animal groups, an important cause of the NSC apoptosis is Bax. In paraventricular nucleus (PVN), of the greater importance is a decrease of the anti-apoptotic protection. Hence, misbalance of synthesis of proteins of the Bcl-2 family plays an important role in development of senescent apoptosis.
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Original Russian Text © E. D. Bazhanova, K. I. Pavlov, I. G. Popovich, V. N. Anisimov, 2009, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2009, Vol. 45, No. 5, pp. 518–523.
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Bazhanova, E.D., Pavlov, K.I., Popovich, I.G. et al. Ontogenetic peculiarities of regulation of apoptosis of hypothalamic neurosecretory cells in TNF-knockout mice. J Evol Biochem Phys 45, 627–633 (2009). https://doi.org/10.1134/S0022093009050107
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DOI: https://doi.org/10.1134/S0022093009050107