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Publication Detail

Title: Role of Ca(2+) in the regulation of nickel-inducible Cap43 gene expression.

Authors: Salnikow, K; Kluz, T; Costa, M

Published In Toxicol Appl Pharmacol, (1999 Oct 15)

Abstract: We have recently cloned a gene, Cap43, that was significantly induced by exposure to nontoxic levels of both water-soluble and -insoluble Ni(2+) compounds. In this paper, we utilized the expression levels of this gene as a tool to identify second messengers involved in nickel-inducible transcription. We report here that the Ca(2+) ionophore A23187 substantially stimulated Cap43 gene expression. In addition, we found that BAPTA-AM, a specific chelator of free intracellular Ca(2+), consistently attenuated the induction of Cap43, indicating that elevation of intracellular Ca(2+) was essential for this response. TPEN, a chelator of heavy metals, such as Ni(2+) with a very low affinity for Ca(2+), did not attenuate Cap43 induced by Ni or calcium ionophore, suggesting that elevations of Ca(2+) but probably not elevations of other metal ions were involved in the induction of Cap43. A direct measurement of Ca(2+) levels using the fluorescent probe Fluo-3 AM showed elevations of free intracellular Ca(2+) in Ni-treated cells. A strong induction of Cap43 by okadaic acid suggested the involvement of a serine/threonine phosphorylation in a signaling pathway that was presumably activated by Ni and that led to enhanced Cap43 gene expression. However, calcium-dependent protein kinase(s) involved in the nickel-activated signaling pathway remains to be identified.

PubMed ID: 10527911 Exiting the NIEHS site

MeSH Terms: Calcium Channel Blockers/pharmacology*; Calcium/analysis; Calcium/metabolism*; Cell Cycle Proteins; Cell Line; Cells, Cultured; Endothelium, Vascular/drug effects; Gene Expression Regulation/drug effects*; Homocysteine/pharmacology; Humans; Intracellular Signaling Peptides and Proteins; Nickel/pharmacology*; Phosphorylation; Protein Biosynthesis*; Proteins/genetics

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