Abstract
The growth hormone (GH)-responsive cytochrome P450 (CYP) 2C11 is down-regulated in vitamin A-deficient (VAD) rat liver. This study assessed the impact of a VAD diet on the hepatic Janus kinase-Signal Transducers and Activators of Transcription (JAK-STAT) system that mediates GH signalling. Nuclear tyrosine- and serine-phosphorylated STAT5 accumulated in VAD liver, whereas nuclear JAK2 tyrosine kinase and SHP-1 phosphatase were decreased. Tyrosine-phosphorylated SHP-1 was decreased to 36+/-14% of control (P<0.01), indicating its impaired activation in VAD liver. Episodic GH pulses increased nuclear phospho-STAT5, especially in control liver, but nuclear phospho-JAK2 and phospho-SHP-1 were not restored. CYP2C11 protein and testosterone 16alpha-hydroxylation were decreased in VAD liver to 67+/-16% and 76+/-19% of control, and were further decreased by GH to 32+/-8% and 30+/-14% of control. Thus, hypo-responsiveness of JAK-STAT in VAD liver is associated with impaired nuclear phospho-STAT dephosphorylation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Aryl Hydrocarbon Hydroxylases / metabolism
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Cell Nucleus / chemistry
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Cell Nucleus / metabolism*
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Cytochrome P450 Family 2
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DNA-Binding Proteins / analysis
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DNA-Binding Proteins / metabolism*
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Growth Hormone / physiology
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Intracellular Signaling Peptides and Proteins
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Janus Kinase 2
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Liver / metabolism*
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Male
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Milk Proteins / analysis
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Milk Proteins / metabolism*
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Phosphorylation
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases / metabolism
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Protein-Tyrosine Kinases / metabolism*
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Proto-Oncogene Proteins / metabolism*
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Rats
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Rats, Wistar
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STAT5 Transcription Factor
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Serine / metabolism
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Signal Transduction
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Steroid 16-alpha-Hydroxylase / metabolism
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Testosterone / metabolism
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Trans-Activators / analysis
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Trans-Activators / metabolism*
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Tyrosine / metabolism
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Vitamin A / metabolism
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Vitamin A Deficiency / genetics
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Vitamin A Deficiency / metabolism*
Substances
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DNA-Binding Proteins
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Intracellular Signaling Peptides and Proteins
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Milk Proteins
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Proto-Oncogene Proteins
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STAT5 Transcription Factor
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Trans-Activators
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Vitamin A
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Testosterone
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Tyrosine
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Serine
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Growth Hormone
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Aryl Hydrocarbon Hydroxylases
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CYP2C11 protein, rat
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Cytochrome P450 Family 2
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Steroid 16-alpha-Hydroxylase
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Protein-Tyrosine Kinases
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Jak2 protein, rat
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Janus Kinase 2
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases
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Ptpn6 protein, rat