Participation of FAS- and TNF-Dependent Pathways in Apoptosis Mechanisms in Hypothalamus in Physiological and Pathological Aging

AbstractCellular resistance to apoptosis can be related to the activity of cytokine-dependent signaling. Thus, the goal of the work is to study the mechanisms of cytokine-dependent, FAS/TNF-mediated regulation of apoptosis of neurosecretory cells in physiological and pathological (overexpression of the oncogene HER-2/Neu) aging. Transgenic, accelerated-aged HER-2/Neu mice of different ages and wild-type FVB/N mice were examined. The apoptosis level of neurons in hypothalamic sections (supraoptic and paraventricular nuclei) (TUNEL) and the expression of caspase-8, CD178 (FASL), FAS, FADD, and TRADD (Western blotting) was determined. It is shown that a proinflammatory component participates in the aging process. The expression ofFAS, adapter proteins associated with the death domain (FADD and TRADD), and caspase-8 is activated in the hypothalamus in FVB/N (wild-type) mice during aging, and it correlates with an increase in the apoptosis level. HER-2/Neu expression leads to suppression of the extrinsic apoptotic pathway. In this case, the reception of an apoptotic signal (FAS-receptor expression) and its further transmission (expression of FADD and TRADD) is suppressed. However, a sufficiently high TRADD expression in young transgenic mice and an increased expression of TNF- α in old mice can activate one of the survival pathways (NF-κB, ERK or PI3K-AKT). Thus, the HER-2/Neu tyrosine kinase receptor plays a role in the mechanism of cell resistance to age-dependent apoptosis, a...

Source: Advances in Gerontology - October 1, 2020 Category: Geriatrics Source Type: research