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Calcium mediates expression of stress‐response genes in prostaglandin A 2 ‐induced growth arrest
Author(s) -
Choi Augustine M. K.,
Tucker Robert W.,
Carlson Sara G.,
Wiegand Gordon,
Holbrooke Nikki J.
Publication year - 1994
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.8.13.7926370
Subject(s) - gene expression , biology , gene , signal transduction , immediate early gene , messenger rna , calcium in biology , microbiology and biotechnology , intracellular , genetics
We have explored the mechanisms involved in the induction of five stress‐response genes (heme oxygenase [HO], c‐ fos , Egr ‐1, gadd153 , and HSP70 ) in human diploid fibroblasts growth‐arrested by treatment with the antiproliferative prostaglandin A 2 (PGA 2 ). The kinetics of c‐ fos and Egr ‐1 induction were found to be rapid with maximum expression occurring within 60 min of treatment, whereas maximum expression of HO, gadd153 , and HSP70 occurred between 4 and 8 h of treatment. Nuclear run‐on assays and measurements of mRNA clearance in the presence of actinomycin D demonstrated that increases in both the rates of gene transcription and/or mRNA stability contribute to the genetic response to PGA 2 . Although the mechanisms responsible for increasing the mRNA levels differ for the individual genes, additional experiments provided evidence that alterations in intracellular calcium ([Ca 2+ ] i ) levels were important in initiating the genetic response to PGA 2 . PGA 2 treatment resulted in a rapid increase in [Ca 2+ ] i with the dose‐response relationship for Ca 2+ mobilization consistent with that seen for the induction of all five genes. [Ca 2+ ] i chelators that attenuate Ca 2+ mobilization by PGA 2 also blocked the mRNA induction by PGA 2 treatment. Density‐inhibited confluent cells were less responsive than proliferating subconfluent cells with respect to Ca 2+ mobilization after PGA 2 treatment. This was correlated with a lower level of gene induction. These studies support the hypothesis that increased Ca 2+ mobilization is an early and central event in the signal transduction pathway (or pathways) mediating the activation of genes in response to PGA 2 treatment.—Choi, A. M. K., Tucker, R. W., Carlson, S. G., Wiegand, G., Holbrook, N. J. Calcium mediates expression of stress‐response genes in prostaglandin A 2 ‐induced growth arrest. FASEB J. 8: 1048‐1054; 1994.