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Vitamin B6 influences glucocorticoid receptor-dependent gene expression
V E Allgood1, F E Powell-Oliver, J A Cidlowski
1Department of Physiology, University of North Carolina, Chapel Hill 27599-7545.
The Journal of Biological Chemistry
|July 25, 1990
Summary
Vitamin B6 concentration impacts gene expression. High intracellular pyridoxal phosphate (PLP) suppressed glucocorticoid receptor activity, while deficiency enhanced it, revealing a novel regulatory mechanism.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Glucocorticoid hormones regulate gene expression via the glucocorticoid receptor (GR).
- Vitamin B6, in its active form pyridoxal phosphate (PLP), is crucial for various cellular processes.
- The precise role of intracellular vitamin B6 levels in modulating GR function remains largely unexplored.
Purpose of the Study:
- To investigate the influence of intracellular vitamin B6 concentration on glucocorticoid receptor-dependent gene expression.
- To elucidate the mechanism by which vitamin B6 affects GR activity.
Main Methods:
- HeLa S3 cells were transfected with a glucocorticoid-responsive chloramphenicol acetyltransferase (CAT) reporter plasmid.
- Intracellular PLP levels were manipulated using pyridoxine (to increase) and 4-deoxypyridoxine (to decrease).
- CAT activity was measured to assess GR-mediated gene expression following glucocorticoid stimulation.
Main Results:
- Elevated intracellular PLP suppressed glucocorticoid-induced CAT activity.
- Moderate PLP deficiency enhanced GR-mediated gene expression.
- These effects occurred without altering GR mRNA, protein levels, or steroid binding capacity.
- No impact on basal CAT activity or GR-insensitive reporter plasmids was observed.
Conclusions:
- Intracellular vitamin B6 concentration selectively modulates glucocorticoid receptor-dependent gene expression.
- This modulation occurs via a novel mechanism independent of GR concentration or ligand binding.
- Vitamin B6 plays a significant regulatory role in the glucocorticoid signaling pathway.