Effect of TNF-α on SMIT mRNA levels and myo-inositol accumulation in cultured endothelial cells

Mark A. Yorek*, Joyce A. Dunlap, Michael J. Thomas, Patrick R. Cammarata, Cheng Zhou, William L. Lowe

*Corresponding author for this work

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Previously we have shown that hyperosmolarity increases Na+-myo- inositol cotransporter (SMIT) activity and mRNA levels in cultured endothelial cells. Because hyperosmolarity and cytokines, such as tumor necrosis factor-α (TNF-α), activate similar signal transduction pathways, we examined the effect of TNF-α on SMIT mRNA levels and myo-inositol accumulation. In contrast to the effect of hyperosmolarity, TNF-α caused a time- and concentration-dependent decrease in SMIT mRNA levels and myo- inositol accumulation. The effect of TNF-α on myo-inositol accumulation was found in large-vessel endothelial cells (derived from the aorta and pulmonary artery) and cerebral microvessel endothelial cells. In bovine aorta and bovine pulmonary artery endothelial cells, TNF-α activated nuclear factor (NF)-κB. TNF-α also increased ceramide levels, and C2-ceramide mimicked the effect of TNF-α on SMIT mRNA levels and myo-inositol accumulation in bovine aorta endothelial cells. Pyrrolidinedithiocarbamate, genistein, and 7- amino-1-chloro-3-tosylamido-2-hepatanone, compounds that can inhibit NF-κB activation, partially prevented the TNF-α-induced decrease in myo-inositol accumulation. The effect of TNF-α on myo-inositol accumulation was also partially prevented by the protein kinase C inhibitor calphostin C but not by staurosporine. These studies demonstrate that TNF-α causes a decrease in SMIT mRNA levels and myo-inositol accumulation in cultured endothelial cells, which may be related to the activation of NF-κB.

Original languageEnglish (US)
Pages (from-to)C58-C71
JournalAmerican Journal of Physiology - Cell Physiology
Volume274
Issue number1 43-1
DOIs
StatePublished - Jan 1998

Keywords

  • Nuclear factor-κB
  • Sodium myo-inositol cotransporter
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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