Journal article
Opposing effects of tumour necrosis factor α and hyperosmolarity on Na+/myo-inositol co-transporter mRNA levels and myo-inositol accumulation by 3T3-L1 adipocytes
The Biochemical journal, Vol.336(2), pp.317-325
12/01/1998
DOI: 10.1042/bj3360317
PMCID: PMC1219874
PMID: 9820807
Abstract
Tumour necrosis factor α (TNF-α) regulates the transport of myo-inositol in 3T3-L1 adipocytes. Treating 3T3-L1 adipocytes with TNF-α decreases Na+/myo-inositol co-transporter (SMIT) mRNA levels and myo-inositol accumulation in a concentration-and time-dependent manner. TNF-α decreases the V′max for high-affinity myo-inositol transport with little change in the K′m. Studies with actinomycin D suggest that RNA synthesis is required for the TNF-α-induced effect on SMIT mRNA levels. In contrast with the effect of TNF-α, hyperosmolarity increases SMIT mRNA levels and myo-inositol accumulation in 3T3-L1 adipocytes. Hyperosmolarity increases SMIT gene expression as evidenced by the inhibition of hyperosmotic induction of SMIT mRNA levels by actinomycin D, and of myo-inositol accumulation by actinomycin D and cycloheximide. TNF-α and osmotic stress have previously been shown to activate similar signal transduction pathways in mammalian cells. In 3T3-L1 adipocytes, both TNF-α and hyperosmolarity increase mitogen-activated protein kinase kinase pathway activity; however, with the possible exception of c-Jun N-terminal kinase, this pathway does not seem to regulate SMIT mRNA levels or myo-inositol accumulation. TNF-α activates nuclear factor κB (NF-κB) in 3T3-L1 adipocytes but, unlike the effect of TNF-α on cultured endothelial cells, NF-κB does not seem to contribute to the regulation by TNF-α of SMIT gene expression in 3T3-L1 adipocytes. Therefore other signal transduction pathways must be considered in the regulation by TNF-α of SMIT mRNA levels and activity. Thus TNF-α and hyperosmolarity have opposing effects on SMIT mRNA levels and activity in 3T3-L1 adipocytes. Because myo-inositol in the form of phosphoinositides is an important component of membranes and signal transduction pathways, the regulation of myo-inositol metabolism by TNF-α might represent another mechanism by which TNF-α regulates adipocyte function.
Details
- Title: Subtitle
- Opposing effects of tumour necrosis factor α and hyperosmolarity on Na+/myo-inositol co-transporter mRNA levels and myo-inositol accumulation by 3T3-L1 adipocytes
- Creators
- Mark A YOREK - Department of Internal Medicine, University of Iowa, Diabetes Endocrinology Research Center and Veterans Affairs Medical Center, Iowa City, IA 52246, U.S.AJoyce A DUNLAP - Department of Internal Medicine, University of Iowa, Diabetes Endocrinology Research Center and Veterans Affairs Medical Center, Iowa City, IA 52246, U.S.AWilliam L LOWE - Department of Medicine, Northwestern University Medical School and Veterans Affairs Chicago Healthcare System Lakeside Division, Chicago, IL 60611, U.S.A
- Resource Type
- Journal article
- Publication Details
- The Biochemical journal, Vol.336(2), pp.317-325
- DOI
- 10.1042/bj3360317
- PMID
- 9820807
- PMCID
- PMC1219874
- ISSN
- 0264-6021
- eISSN
- 1470-8728
- Language
- English
- Date published
- 12/01/1998
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094716602771
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