Journal article
Effect of TNF-α on SMIT mRNA levels andmyo-inositol accumulation in cultured endothelial cells
The American journal of physiology, Vol.274(1), pp.C58-C71
01/1998
DOI: 10.1152/ajpcell.1998.274.1.C58
PMID: 9458713
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-alpha (TNF-alpha), activate similar signal transduction pathways, we examined the effect of TNF-alpha on SMIT mRNA levels and myo-inositol accumulation. In contrast to the effect of hyperosmolarity, TNF-alpha caused a time- and concentration-dependent decrease in SMIT mRNA levels and myo-inositol accumulation. The effect of TNF-alpha 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-alpha activated nuclear factor (NF)-kappa B. TNF-alpha also increased ceramide levels, and C2-ceramide mimicked the effect of TNF-alpha 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-kappa B activation, partially prevented the TNF-alpha-induced decrease in myo-inositol accumulation. The effect of TNF-alpha 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-alpha causes a decrease in SMIT mRNA levels and myo-inositol accumulation in cultured endothelial cells, which may be related to the activation of NF-kappa B.
Details
- Title: Subtitle
- Effect of TNF-α on SMIT mRNA levels andmyo-inositol accumulation in cultured endothelial cells
- Creators
- Mark A Yorek - Department of Internal Medicine, University of Iowa, Iowa City 52246, USAJoyce A DunlapMichael J ThomasPatrick R CammarataCheng ZhouWilliam L Lowe Jr
- Resource Type
- Journal article
- Publication Details
- The American journal of physiology, Vol.274(1), pp.C58-C71
- DOI
- 10.1152/ajpcell.1998.274.1.C58
- PMID
- 9458713
- ISSN
- 0002-9513
- eISSN
- 2163-5773
- Grant note
- DK-25295 / NIDDK NIH HHS DK-45453 / NIDDK NIH HHS
- Language
- English
- Date published
- 01/1998
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094589602771
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