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.
No takes yet. Share an insight, caveat, or question.
Yorek et al. (1998) studied this question.
Synapse has enriched 4 closely related papers on similar clinical questions. Consider them for comparative context: