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Published on: September 21, 2011
Function of nuclear steroid receptors in apoptosis: role of ursodeoxycholic acid
Joana D Amaral1, Susana Solá2, Clifford J Steer3
1a Research Institute for Medicines & Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal. jamaral@ff.ul.pt.
Abstract:
Nuclear steroid receptors such as the glucocorticoid and the mineralocorticoid receptors modulate apoptosis in different cell types through transactivation-dependent and -independent mechanisms. They are involved in both the induction and prevention of apoptosis depending on cell type. However, it is unclear how nuclear steroid receptors can affect expression of the same gene in opposing ways for different cells. In addition to their function as modulators of gene expression, nuclear steroid receptors often act as nuclear transporters of other regulatory molecules, thus indirectly regulating several apoptosis-related genes. Curiously, nuclear steroid receptors are thought to cooperate with the antiapoptotic endogenous bile acid, ursodeoxycholic acid, to prevent programmed cell death. The next decade will almost certainly unveil the remarkable role of nuclear steroid receptors in modulating the life and death struggle of cells and organ systems in human development and function.
Insights
Nuclear steroid receptors regulate cell death pathways, acting as both inducers and preventers of apoptosis. Their complex roles, including gene expression modulation and transport functions, are crucial for cellular life and death.
Area of Science:
- Molecular Biology
- Cell Biology
- Endocrinology
Background:
- Nuclear steroid receptors, including glucocorticoid and mineralocorticoid receptors, are key regulators of apoptosis.
- These receptors influence programmed cell death through both transactivation-dependent and -independent mechanisms.
- Their precise role in modulating apoptosis varies significantly across different cell types.
Purpose of the Study:
- To explore the multifaceted roles of nuclear steroid receptors in apoptosis.
- To investigate the mechanisms by which these receptors can oppose gene expression in different cellular contexts.
- To highlight the potential of nuclear steroid receptors as therapeutic targets.
Main Methods:
- Review of existing literature on nuclear steroid receptors and apoptosis.
- Analysis of transactivation-dependent and -independent signaling pathways.
- Examination of the interaction between nuclear steroid receptors and other regulatory molecules.
Main Results:
- Nuclear steroid receptors can either induce or prevent apoptosis, depending on the cell type.
- Receptors modulate gene expression through direct and indirect mechanisms, including acting as nuclear transporters.
- Cooperation with molecules like ursodeoxycholic acid suggests an antiapoptotic function.
Conclusions:
- Nuclear steroid receptors play a complex and critical role in regulating cellular life and death.
- Further research is needed to fully elucidate their mechanisms and therapeutic potential.
- Understanding these pathways is vital for human development and physiological function.
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