ArticleJournal of cellular physiology2008
Alpha-1 adrenergic receptor transactivates signal transducer and activator of transcription-3 (Stat3) through activation of Src and epidermal growth factor receptor (EGFR) in hepatocytes.
Article in Journal of cellular physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 59 citations in OpenAlex.
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- Sympathetic nervous system in tumor progression and metabolic regulation: mechanisms and clinical potential.Journal of translational medicine · 2025Review
- Effects of prazosin treatment on liver enzymes are moderated by alcohol withdrawal symptoms in individuals with alcohol use disorder.Alcohol, clinical & experimental research · 2024Article
- Liver regeneration biology: Implications for liver tumour therapies.World journal of clinical oncology · 2021Review
- Liver regeneration: biological and pathological mechanisms and implications.Nature reviews. Gastroenterology & hepatology · 2021Review
- Pathophysiologic Role of Neurotransmitters in Digestive Diseases.Frontiers in physiology · 2021Review
- Hormonal Contribution to Liver Regeneration.Mayo Clinic proceedings. Innovations, quality & outcomes · 2020Review
- Norepinephrine-stimulated HSCs secrete sFRP1 to promote HCC progression following chronic stress via augmentation of a Wnt16B/β-catenin positive feedback loop.Journal of experimental & clinical cancer research : CR · 2020Article
- Constitutive SRC-mediated phosphorylation of pannexin 1 at tyrosine 198 occurs at the plasma membrane.The Journal of biological chemistry · 2019Article
- microRNA-133a attenuates cardiomyocyte hypertrophy by targeting PKCδ and Gq.Molecular and cellular biochemistry · 2018Article
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- Inhibition of hedgehog signaling ameliorates hepatic inflammation in mice with nonalcoholic fatty liver disease.Hepatology (Baltimore, Md.) · 2016Article
- Insights into cardio-oncology: Polypharmacology of quinazoline-based α1-adrenoceptor antagonists.World journal of cardiology · 2015Review
- Aberrant α-adrenergic hypertrophic response in cardiomyocytes from human induced pluripotent cells.Stem cell reports · 2014Article
- Article
- GM-CSF protects rat photoreceptors from death by activating the SRC-dependent signalling and elevating anti-apoptotic factors and neurotrophins.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2012Article
- Gene deletions and amplifications in human hepatocellular carcinomas: correlation with hepatocyte growth regulation.The American journal of pathology · 2012Article
- Activation of alpha(1) -adrenergic receptors stimulate the growth of small mouse cholangiocytes via calcium-dependent activation of nuclear factor of activated T cells 2 and specificity protein 1.Hepatology (Baltimore, Md.) · 2011Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Hepatocytes express adrenergic receptors (ARs) that modulate several functions, including liver regeneration, hepatocyte proliferation, glycogenolysis, gluconeogenesis, synthesis of urea and fatty acid metabolism. Adrenergic hepatic function in adults is mainly under the control of alpha(1)-ARs; however, the mechanism through which they influence diverse processes remains incompletely understood. This study describes a novel alpha(1)-AR-mediated transactivation of signal transducer and activator of transcription-3 (Stat3) in primary and transformed hepatocytes. Treatment of primary rat hepatocytes with the alpha(1)-AR agonist, phenylephrine (PE), induced a rapid phosphorylation of Stat3. PE also increased Stat3 phosphorylation, DNA binding and transcription activity in transformed human hepatocellular carcinoma cells (Hep3B). The PE-induced Stat3 phosphorylation, DNA binding and reporter activity were completely blocked by the selective alpha(1)-AR antagonist, prazosin. In addition, transfection of Hep3B cells with human alpha(1B)-AR expression vector also enhanced Stat3 phosphorylation and reporter activity. Moreover, overexpression of RGS2, a protein inhibitor of G(q/11) signaling, blocked PE-induced Stat3 phosphorylation and reporter activity. The observations that PE induced the formation of c-Src-Stat3 binding complex and phosphorylation of epidermal growth factor receptor (EGFR) and that inhibiting Src and EGFR prevented PE-induced Stat3 activation indicate the involvement of Src and EGFR. Taken together, these observations demonstrate a novel alpha(1)-AR-mediated Stat3 activation that involves G(q/11), Src, and EGFR in hepatic cells.
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