Temperature dependence of glucocorticoid binding in sensitive and refractory murine leukaemia cells

Berg, J.D. van den; Smets, L. A.; Elshout, Marion M. van den; Geel, I. P. J. van; Janssen, Manon

doi:10.1016/0145-2126(93)90010-i

Cited by 7 publications

(12 citation statements)

References 13 publications

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“…Because of the long induction time, the evidence for a causal involvement of agonist-free GC receptor in low serum-induced apoptosis was only indirect, namely the cross-resistance of H.2 cells to low serum, DEX and heat and the simultaneous sensitization to these conditions by the drug MIBG ( Figure 6). Similar to what was observed in related L1210 variants, 22 MIBG restored the in vitro activation of cytosolic GC receptors from H.2 cells and promoted the loss of 3 H-DEX binding after heat shock.…”

Section: Discussionsupporting

confidence: 80%

“…In related L1210 lymphoma cells, MIBG abrogates resistance to DEX, restores the in vitro activation of cytosolic receptors and converts the antagonist RU484 into a potent agonist. 22 MIBG also sensitized resistant S49 H.2 cells not only to DEX but also to low serum that heat shock, but not so to cold shock ( Figure 6). To assess for nonspecific effects that may have resulted from the documented antimitochondrial activity of MIBG, 30 control studies were performed with the mitochondrial inhibitor rotenone which also acts on complex I of mitochondrial respiration and has comparable effects on cellular energy charge in a concentration of 10 −6 M. 14 MIBG and rotenone alone were minimally toxic to both S49 and H.2 cells (Figure 6, controls) but rotenone did not abrogate resistance to DEX and low serum.…”

Section: Abrogation Of Cross-resistance To Dex and Stress Factorsmentioning

confidence: 94%

“…Activation in vitro was assayed as the binding to DNA-cellulose of cytosolic receptors, first complexed with 3 H-DEX for 2 h at 0°C and subsequently heated at 20°C as described previously. 22 At indicated times, aliquots of the cytosol were passed on mini-columns of DNA-cellulose (Pharmacia, Uppsala, Sweden) or DEAE-sepharose to determine activated, DNA-binding 3 H-DEX-labelled proteins in per cent of total labelled protein, retained by DEAE.…”

Section: Glucocorticoid Receptor Assaysmentioning

confidence: 99%

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

et al. 1998

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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 factors Il-2, IL-4 or IL-9. The results suggest that ligand-independent activation of the GC receptor is a central signalling and controlling event in some forms of stress-induced apoptosis, assigning a novel function to the GC receptor in the regulation of lymphoid and leukemic cell numbers.

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Section: Discussionsupporting

confidence: 80%

Section: Abrogation Of Cross-resistance To Dex and Stress Factorsmentioning

confidence: 94%

Section: Glucocorticoid Receptor Assaysmentioning

confidence: 99%

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

et al. 1998

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“…In agreement with this, we found that differences in binding affinities between sensitive and resistant childhood leukaemia samples are masked when assayed at room temperature. After modification of the ligand binding assay as described by (Van den Berg et al , 1993), we were able to demonstrate that, apart from lower GR levels, T‐lineage ALL (T‐ALL) and AML samples (leukaemia subgroups relatively resistant to GC‐induced cell kill) had receptors with reduced affinity at 37°C (Haarman et al, 2002).…”

Section: The Glucocorticoid Receptormentioning

confidence: 99%

Glucocorticoid resistance in childhood leukaemia: mechanisms and modulation

2003

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“…Van den Berg et al 7 suggested that thermolability of the receptor-ligand complex might be a cause of GC resistance. In refractory and fully resistant murine cell lines non-saturating, low affinity binding of steroid occurred when assayed at 37°C.…”

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confidence: 99%

In vitro glucocorticoid resistance in childhood leukemia correlates with receptor affinity determined at 37°C, but not with affinity determined at room temperature

et al. 2002

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Leukemia Figure 1PCR analyses of viral genomes. Lane 1, patient 1 (ATLL lymphoma type); lane 2, patient 2 (ATLL acute type); lane 3, positive control; lane 4, H 2 O; M, molecular weight markers. Positive controls used are MT-2 for HTLV-1, Kaposi's sarcoma tissue for HHV-8, Raji for EBV, and Katata for HHV-6. ␤-globin was used as an internal control. The amplification products were electrophoresed in 2.0% agarose gels, stained with ethidium bromide, and visualized on an UV transilluminator.In vitro glucocorticoid resistance in childhood leukemia correlates with receptor affinity determined at 37°C, but not with affinity determined at room temperature Leukemia (2002) 16, 1882-1884. doi:10.1038/sj.leu.2402606 TO THE EDITOR Glucocorticoid (GC) resistance in childhood acute lymphoblastic leukemia (ALL) is a major adverse prognostic factor. 1 In cell line models resistance to glucocorticoids is almost invariably associated with low glucocorticoid receptor (GR) expression or decreased GR affinity. 2 By contrast, attempts to correlate clinical responses in individual leukemia patients with receptor status have proven to be of limited clinical value. [3][4][5] In addition, expression levels of the GR were similar in pediatric acute myeloid leukemia (AML) and ALL samples. 6 These observations have led many researchers to believe that clinical resistance to steroids is due to more subtle changes in receptor properties or due Correspondence: EG Haarman,

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Temperature dependence of glucocorticoid binding in sensitive and refractory murine leukaemia cells

Cited by 7 publications

References 13 publications

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

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

Glucocorticoid resistance in childhood leukaemia: mechanisms and modulation

In vitro glucocorticoid resistance in childhood leukemia correlates with receptor affinity determined at 37°C, but not with affinity determined at room temperature

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