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Regulation of 1α,25‐dihydroxyvitamin D 3 synthesis in macrophages from arthritic joints by phorbol ester, dibutyryl‐cAMP and calcium ionophore (A23187)
Author(s) -
Yuan J.Y.,
Freemont A.J.,
Mawer E.B.,
Hayes M.E.
Publication year - 1992
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(92)81370-2
Subject(s) - ionophore , activator (genetics) , calcium , protein kinase c , phorbol , endocrinology , medicine , chemistry , calcium in biology , intracellular , phorbol ester , protein kinase a , microbiology and biotechnology , enzyme , biochemistry , biology , receptor
Phorbol 12‐myristate 13‐acetate (100 nM), a potent protein kinase C and macrophage activator, has a biphasic affect on 25(OH)D 3 ‐1α‐hydroxylase activity in synovial fluid macrophages from arthritis patients, After 5 h, 1α,25(OH)D 3 synthesis fell from 5.2 ± 0.1 to 1.6 ± 0.2 pmol/h per 10 6 cells, however, after 24 h and 48 h, synthesis increased to 17.4 ± 0.3 and 22.3 ± 1.4 pmol/h per 10 6 cells, respectively. Although an independent short‐term mechanism is suggested, protein kinase C may promote macrophage activation, thus increasing long‐term 25(OH)D 3 ‐1α‐hydroxylase expression. Intracellular calcium and cAMP are unlikely to activate the enzyme, since 0.1 μM of the calcium ionophore, A23187, and 1 mM dibutyryl‐cAMP inhibited synthesis by 87% and 79%, respectively, after 24 h.