Function of nuclear steroid receptors in apoptosis: role of ursodeoxycholic acid

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.

Keywords::

• apoptosis
• Bcl-2 family
• glucocorticoid receptor
• mineralocorticoid receptor
• nuclear steroid receptors
• nuclear trafficking
• ursodeoxycholic acid

Acknowledgements

Supported by grants POCI/SAU-FCF/62479/2004 and POCI/SAU-MMO/57936/2004 from Fundação para a Ciência e a Tecnologia (FCT), Lisbon, Portugal (to CMPR). Joana Amaral and Susana Solá are recipients of PhD (SFRH/BD/17799/2004) and postdoctoral (SFRH/BPD/20834/2004) fellowships, respectively, from FCT. The authors thank all the members of the laboratory for critical reading of the manuscript.