Involvement of the glucocorticoid receptor in stress-induced apoptosis of leukemic cells

Leukemia
L A SmetsJ van den Berg

Abstract

Glucocorticoid (GC) hormones induce apoptosis in lymphoid and leukemic cells by binding and activating cytosolic GC receptors. Because physiological stress often causes hormone-free GC receptor activation, we have investigated if stress-induced apoptosis of lymphoid cells is also mediated by the activation of the GC receptor pathway. In S49 T lymphoma cells, heat shock and deprivation of growth factors or nutrients caused nuclear translocation and loss of agonist binding capacity of GC receptors, similar to that in cells incubated with the glucocorticoid dexamethasone (DEX). In variant S49 H.2 cells, cross-resistance to DEX, temperature shocks and growth factor deprivation were associated with a higher threshold for hormone-dependent and -independent receptor activation in situ and with impaired in vitro activation of cytosolic receptors. Cross-resistance to DEX, low serum and heat shock was abrogated, however, by pharmacological sensitization of GC receptor activation with the drug meta-iodobenzylguanidine (MIBG). Sensitive S49 cells and resistant variants did not differ in the expression levels of the apoptosis-regulating genes bax, bad, bcl-X and bcl-2, the status of the p53 gene nor in a different requirement for the growth...Continue Reading

Citations

Sep 6, 2000·Journal of the European Academy of Dermatology and Venereology : JEADV·U ButtoniS Calvieri
Aug 7, 2008·PloS One·Jinze XuChristiaan Leeuwenburgh
Oct 13, 2000·American Journal of Physiology. Cell Physiology·L YanP A Insel
Oct 16, 2001·American Journal of Physiology. Cell Physiology·L Zhang, P A Insel

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