1Alpha,25-dihydroxyvitamin D3 up-regulates Bcl-2 expression and protects normal human thyrocytes from programmed cell death.
Apoptosis is thought to play an important role in the pathogenesis of autoimmune thyroid disease. 1alpha,25-dihydroxyvitamin D3 (VD3) has been shown to suppress several autoimmune diseases. However, the mechanism by which VD3 has these effects is not known. We evaluated the alterations in apoptosis, induced by VD3. Thyrocytes were treated with VD3, and the expression of the Bcl-2 family molecules was studied at both the messenger RNA and protein levels. It was found that VD3 significantly induced the expression of Bcl-2 messenger RNA and protein in thyrocytes but had no effect on the expression of Bcl-xl and Bax. The increase in Bcl-2 expression, mediated by VD3, correlated with protection of thyrocytes against the induction of apoptosis by either staurosporine or UV irradiation. VD3-induced increases in the expression of Bcl-2 could be mimicked by VD3 analogs with high nuclear receptor affinity, but not by analogs only with nongenomic actions. These data indicate a role for Bcl-2 in the regulation of apoptosis in thyrocytes and raise the possibility that VD3 or its agonists may have therapeutic benefit in thyroid disorders.
Wang
S H
SH
Department of Medicine, University of Michigan Medical School, Ann Arbor 48109-0648, USA.
Koenig
R J
RJ
Giordano
T J
TJ
Myc
A
A
Thompson
N W
NW
Baker
J R
JR
D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D019254:Genes, bcl-2 / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology*; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494826:BAX protein, human; C494811:BCL2L1 protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D002117:Calcitriol; D019311:Staurosporine