Premium
Protein kinase C signaling modulates 1alpha,25(OH)2D3‐regulated CYP24 gene expression in differentiated Caco‐2 cells
Author(s) -
Jiang Yan,
Fleet James C.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1108
Subject(s) - protein kinase c , p38 mitogen activated protein kinases , protein kinase a , kinase , microbiology and biotechnology , chemistry , mapk/erk pathway , caco 2 , biology , cell , biochemistry
A number of kinase pathways have been found to modulate the genomic action of 1α, 25 dihydroxyvitamin D 3 (1,25 D) but this has not been well studied in enterocytes, a primary 1,25 D target cell. We examined the role of protein kinase C (PKC) on 1,25 D action in differentiated Caco‐2 cells, an established model for 1,25 D‐mediated intestinal calcium (Ca) absorption. Activation of PKC with phorbol ester (PMA 100 nM, 5 min pre‐treatment) significantly enhanced 1,25 D (10 nM, 2 h)‐induced accumulation of 24‐hydroxylase (CYP24) mRNA by 160% but had no impact on induction of the mRNA for the apical Ca channel TRPV6. Inhibition of Ca‐dependent PKC isoforms (2 and 10 μM Go6976) reduced basal (by 40 and 70%) and PMA‐enhanced effects of 1,25 D on CYP24 mRNA accumulation. MAPK family members ERK1/2 and p38 kinase were activated by PMA treatment (100 nM, 5min). However, while MEK (10 μM U0126) and p38 kinase (8.75 μM SB202190) inhibition reduce 1,25 D‐mediated CYP24 mRNA accumulation by 50–60%, only the p38 inhibitor reduced the PMA effect on 1,25 D action (by 40%). Thus, our data show that PMA enhances 1,25 D‐induced CYP24 mRNA accumulation through activation of Ca‐dependent PKC isoforms and p38 kinase. In addition, the induction of CYP24 mRNA by 1,25 D in enterocytes is dependent upon PKC, p38 kinase and ERK 1/2. However, the molecular targets for these interactions remain to be determined. Supported by NIDDK Award DK54111 to JCF.