-P. 4807-4816.

26. Zhou B.P., Hu M.C., Miller S.A. et al. HER-2/neu blocks tumor necrosis factor-induced apoptosis via the Akt/NF-kappaB pathway //J. Biol. Chem.-2000.-Vol. 275, № 11.-P. 8027­8031.

Adv. Gerontol.-2007.-Vol. 20, № 4.-P. 31-35

E.D. Bazhanova, V.N. Molodtsov¹,1.G. Popovich², V.N. Anisimov² apoptosis regulation in hypothalamic neurosecretory cells of her2/neu transgenic

mice in ontogenesis

I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 44 pr. Thoreza, St.Petersburg 194223, Russia; e-mail: bazhanovae@mail.ru; ¹Graduate School of Biomedical Sciences-Stratford Division, University of Medicine and Dentistry of New Jersey, Stratford, New Jersey, USA, ²N.N. Petrov Research Institute

of Oncology, St.Petersburg, Russia

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 (Вах, с-Raf) in comparison with apoptosis level and functional activity (vasopressin concentration) in neuroendocrine system. Besides, we studied the level of 17p-estradiol in blood plasma. ^-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. 17p-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.

Key words: apoptosis, aging, HER2/neu transgenic mice, neurosecretory cells, Вах, vasopressin, estradiol, с-Raf-L

35

УСПЕХи геронтологии • 2007 • Т. 20, № 4

© А.А. Москалев, Е.Н. Плюснина, 2007 г УДК 575.113:612.67

Успехи геронтол

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35