| First Author | Martins TC | Year | 1998 |
| Journal | Immunology | Volume | 95 |
| Issue | 3 | Pages | 377-82 |
| PubMed ID | 9824500 | Mgi Jnum | J:50738 |
| Mgi Id | MGI:1309676 | Doi | 10.1046/j.1365-2567.1998.00600.x |
| Citation | Martins TC, et al. (1998) Involvement of c-myc in the resistance of non-obese diabetic mice to glucocorticoid-induced apoptosis. Immunology 95(3):377-82 |
| abstractText | Non-obese diabetic (NOD) mice spontaneously develop insulin-dependent diabetes mellitus (IDDM) as a consequence of autoimmune aggression of beta cells of the endocrine pancreas by T cells. T lymphocytes of NOD mice are resistant to apoptosis induced by glucocorticoids, or by starving or DNA-damaging treatments, a feature that was interpreted as being linked to escape of autoreactive T cells from thymic negative selection. c-myc is one of the gene targets of glucocorticoids (GC), its expression being down-regulated by the activated GC-GC receptor complex. We investigated here whether expression of Myc protein, in response to dexamethasone stimulation, was the same in NOD mice and in non-autoimmune strains, namely NON, BALB/c and C57Bl.6. We found a consistent increase in the levels of Myc protein after GC-treatment of lymphocytes of NOD mice, a finding that was in contrast to the down-regulation of c-myc that we observed in lymphocytes from mice not prone to diabetes. We also report that, rather than a absolute resistance to GC-induced cell death, NOD mice display a delayed apoptotic response to GC. We propose that the resistance of NOD mice lymphocytes to GC-induced apoptosis is because of inhibition of the repressive action of GC-GR complexes at the level of c-myc transcription. This deficient action of GC-GR results in increased production of nuclear Myc protein, peculiar to NOD mice cells, following their treatment with GC. |
