[Apoptosis regulation in hypothalamic neurosecretory cells of HER2/neu transgenic mice in ontogenesis].
Tyrosine kinase receptor HER2/neu plays an important role in a number of processes including carcinogenesis. The oncogenic characteristics of HER2/neu are associated with its ability to affect a variety of apoptotic pathways creating, this way, an antiapoptotic environment in the cells overexpressing this protein. The aim of our work was to investigate the features of apoptosis regulation in hypothalamic neurosecretory cells of HER2/neu transgenic mice in aging. We detected the apoptosis protein expression (Bax, c-Raf) in comparison with apoptosis level and functional activity (vasopressin concentration) in neuroendocrine system. Besides, we studied the level of 17beta-estradiol in blood plasma. 17beta-estradiol is one of possible antiapoptotic factors in neurons. We show that the apoptosis of neuroendocrine cells increases in aged wild type mice, but not in HER2/neu ones. Recently we obtained that the mechanism of apoptosis suppression in transgenic mice is the block of p53-dependent apoptosis cascade, and it is the cause of caspadse-8 decrease and dysregulation of Bcl-2 and Mcl-1 antiapoptotic protein synthesis. In this study it has been shown that Bax concentration decreases and c-Raf-1 expression does not change. 17beta-estradiol does not decrease in plasma of aged transgenic mice and it is the factor, which can play a positive role in neuroendocrine cells survival. Besides, the vasopressin synthesis increases in young and old HER2 mice. These facts result in the increased survival of neurosecretory cells in old transgenic mice.
Bazhanova
E D
ED
Molodtsov
V N
VN
Popovich
I G
IG
Anisimov
V N
VN
D000375:Aging / Q000235:genetics / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D004958:Estradiol / Q000097:blood; D007031:Hypothalamus / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009490:Neurosecretory Systems / Q000378:metabolism / Q000473:pathology*; D019908:Proto-Oncogene Proteins c-raf / Q000096:biosynthesis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D014667:Vasopressins / Q000097:blood; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
D004958:Estradiol; D019908:Proto-Oncogene Proteins c-raf; D018719:Erb-b2 Receptor Tyrosine Kinases; D014667:Vasopressins; D051028:bcl-2-Associated X Protein; C494827:Bax protein, mouse; C524056:Erbb2 protein, mouse