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Comparison of glucocorticoid-mediated changes in the expression and function of rat hepatocyte gap junctional
A P Kwiatkowski1, T K Baker, J E Klaunig
1Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis 46202.
Abstract:
Gap junctional intercellular communication (GJIC) is often modulated by chemical carcinogens and during carcinogenesis, in part, through changes in gap junction mRNA levels. However, the mechanisms by which gap junction mRNA levels are altered in either normal or cancer cells are largely unknown. Since glucocorticoids are potent modulators of gene expression and stability, we have investigated the effects of these hormones on GJIC and gap junction mRNA expression in rat hepatocytes cultured in three different media. Addition of dexamethasone to cultures of rat hepatocytes resulted in a maintenance of GJIC and both major liver gap junctional mRNAs, connexin (Cx)26 and Cx32, at levels above those in hepatocytes cultured in glucocorticoid-free media. In addition, hepatocytes cultured without dexamethasone for 24 h could be induced to communicate and increase Cx mRNA levels by the addition of dexamethasone to their medium. These media-independent changes in GJIC and gap junction mRNA levels by dexamethasone warrant further investigations into their mechanisms of action and the potential therapeutic value of glucocorticoids in the treatment of cancer.
Insights
Glucocorticoids like dexamethasone maintain gap junction communication and connexin mRNA levels in rat liver cells. This hormone-induced effect on gap junctional intercellular communication (GJIC) suggests potential cancer therapeutic applications.
Area of Science:
- Cellular Biology
- Molecular Biology
- Endocrinology
Background:
- Gap junctional intercellular communication (GJIC) is crucial for cell function and is often altered during carcinogenesis.
- Mechanisms regulating gap junction mRNA levels in normal and cancer cells remain largely unknown.
- Glucocorticoids are known potent modulators of gene expression and mRNA stability.
Purpose of the Study:
- To investigate the effects of glucocorticoids on GJIC and gap junction mRNA expression in rat hepatocytes.
- To explore the potential role of dexamethasone in modulating connexin (Cx) mRNA levels and GJIC.
Main Methods:
- Culturing rat hepatocytes in three different media, with and without dexamethasone.
- Measuring GJIC levels in cultured hepatocytes.
- Quantifying major liver gap junctional mRNAs, connexin (Cx)26 and Cx32, using molecular techniques.
Main Results:
- Dexamethasone addition maintained GJIC and Cx26/Cx32 mRNA levels in rat hepatocytes.
- Hepatocytes cultured without dexamethasone showed increased GJIC and Cx mRNA levels upon dexamethasone addition.
- These effects were observed independently of the culture media used.
Conclusions:
- Glucocorticoids, specifically dexamethasone, significantly influence GJIC and gap junction mRNA expression in rat hepatocytes.
- Dexamethasone maintains and can induce GJIC and connexin mRNA levels, suggesting a regulatory role.
- Further research into the mechanisms and therapeutic potential of glucocorticoids in cancer treatment is warranted.