Dexamethasone-induced Inositol 1,4,5-Trisphosphate Receptor Elevation in Murine Lymphoma Cells Is Not Required for Dexamethasone-mediated Calcium Elevation and Apoptosis*

Glucocorticosteroid hormones, including dexamethasone, have diverse effects on immature lymphocyte function that ultimately lead to cell death. Previous studies established that glucocorticoid-induced alterations in intracellular calcium homeostasis promote apoptosis, but the mechanism by which glucocorticoids disrupt calcium homeostasis is unknown. Through gene expression array analysis, we found that dexamethasone induces a striking elevation of inositol 1,4,5-trisphosphate receptor (IP3R) levels in two murine lymphoma cell lines, WEHI7.2 and S49.A2. IP3R elevation was confirmed at both mRNA and protein levels. However, there was not a strong correlation between IP3R elevation and altered calcium homeostasis in terms of either kinetics or dose response. Moreover, IP3R knockdown, by either antisense or small interfering RNA, did not prevent either calcium disruption or apoptosis. Finally, DT40 lymphoma cells lacking all three IP3R isoforms were just as sensitive to dexamethasone-induced apoptosis as wild-type DT40 cells expressing all three IP3R isoforms. Thus, although alterations in intracellular calcium homeostasis contribute to glucocorticoid-induced apoptosis, these calcium alterations are not directly attributable to IP3R elevation.

• Publication year

  2008

• Venue

  Journal of Biological Chemistry

• Publication date

  2008-04-18

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.M800269200PMID 18272518PMCID PMC2447640
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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