Differential effect of 1(alpha),25-dihydroxyvitamin D(sub 3) on Hsp28 and PKC(beta) gene expression in the phorbol ester-resistant human myeloid HL-525 leukemic cells

摘要

We investigated the effect of 1(alpha),25-dihydroxyvitamin D(sub 3) (1,25-(OH)(sub 2)D(sub 3)) on the expression of the 28-kDa heat shock protein gene (hsp28) and the protein kinase C beta gene (PKC(beta)) in the human myeloid HL-60 leukemic cell variant HL-525, which is resistance to phorbol ester-induced macrophage differentiation. Northern and Western blot analysis showed little or no hsp28 gene expression in the HL-60 cell variant, HL-205, which is susceptible to such differentiation, while a relatively high basal level of hps28 gene expression was observed in the HL-525 cells. However, both cell lines demonstrated heat shock-induced expression of this gene. During treatment with 50-300 nM 1,25-(OH)(sub 2)D(sub 3), a marked reduction of hsp28 gene expression was not associated with heat shock transcription factor-heat shock element (HSF-HSE) binding activity. Our results suggest that the differential effect of 1,25-(OH)(sub 2)D(sub 3) on hsp28 and PKC(beta) gene expression is due to the different sequence composition of the vitamin D response element in the in the promoter region as well as an accessory factor for each gene or that 1,25-(OH)(sub 2)D(sub 3) increases PKC(beta) gene expression, which in turn negatively regulates the expression of the hsp28 gene, or vice versa.