Discovery of Osmo-sensitive Transcriptional Regulation of Human Cytochrome P450 3As (CYP3As) by the Tonicity-Responsive Enhancer Binding Protein (TonEBP/ NFAT5)
نویسندگان
چکیده
Division of Clinical Pharmacology & Toxicology, Department of Paediatrics, Physiology and Experimental Medicine Program, Research Institute, Hospital for Sick Children (K.K., A.I. C., S.U., K.P.T., S.I.); Department of Anatomical and Cellular Pathology, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong, and Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong (B.C.B.K.); and Department of Clinical Pharmacology and Therapeutics, Oita University Faculty of Medicine (K.O.) Molecular Pharmacology Fast Forward. Published on June 28, 2007 as doi:10.1124/mol.107.034504
منابع مشابه
Discovery of osmosensitive transcriptional regulation of human cytochrome P450 3As by the tonicity-responsive enhancer binding protein (nuclear factor of activated T cells 5).
We report the discovery of an osmosensitive transcriptional control of human CYP3A4, CYP3A7, and CYP3A5. Ambient hypertonicity (350-450 mOsmol/kg) increased mRNA expressions of the CYP3A by approximately 10- to 20-fold in human-intestinal C(2)bbe1 cells, followed by an increase of CYP3A protein. Hypotonicity, on the other hand, suppressed CYP3A mRNA levels, indicating that physiological isotoni...
متن کاملTonicity-independent regulation of the osmosensitive transcription factor TonEBP (NFAT5).
Tonicity-responsive enhancer binding protein (TonEBP/nuclear factor of activated T-cells 5 [NFAT5]) is a Rel homology transcription factor classically known for its osmosensitive role in regulating cellular homeostasis during states of hypo- and hypertonic stress. A recently growing body of research indicates that TonEBP is not solely regulated by tonicity, but that it can be stimulated by vari...
متن کاملFyn and p38 signaling are both required for maximal hypertonic activation of the osmotic response element-binding protein/tonicity-responsive enhancer-binding protein (OREBP/TonEBP).
When cells are challenged by hyperosmotic stress, one of the crucial adaptive responses is the expression of osmoprotective genes that are responsible for raising the intracellular level of compatible osmolytes such as sorbitol, betaine, and myo-inositol. This is achieved by the activation of the transcription factor called OREBP (also known as TonEBP or NFAT5) that specifically binds to the os...
متن کاملIncreased reactive oxygen species contribute to high NaCl-induced activation of the osmoregulatory transcription factor TonEBP/OREBP.
The signaling pathways leading to high NaCl-induced activation of the transcription factor tonicity-responsive enhancer binding protein/osmotic response element binding protein (TonEBP/OREBP) remain incompletely understood. High NaCl has been reported to produce oxidative stress. Reactive oxygen species (ROS), which are a component of oxidative stress, contribute to regulation of transcription ...
متن کاملRegulation of TonEBP transcriptional activator in MDCK cells following changes in ambient tonicity.
In response to ambient hypertonicity, TonEBP (tonicity-responsive enhancer binding protein) stimulates certain genes including those encoding cytokines, transporters for organic solutes, and a molecular chaperone. TonEBP is regulated in a bidirectional manner, upregulated by an increase in ambient tonicity while downregulated by a decrease. To investigate the role of intracellular ionic strengt...
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