NO sensitizes rat hepatocytes to proliferation by modifying S-adenosylmethionine levels
| العنوان: | NO sensitizes rat hepatocytes to proliferation by modifying S-adenosylmethionine levels |
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| المؤلفون: | Matías A. Avila, María Luz Martínez Chantar, José M. Mato, M. Ujue Latasa, Elena R. García–Trevijano |
| المصدر: | ResearcherID Dadun. Depósito Académico Digital de la Universidad de Navarra instname |
| بيانات النشر: | Elsevier BV, 2002. |
| سنة النشر: | 2002 |
| مصطلحات موضوعية: | Male, S-Adenosylmethionine, medicine.medical_treatment, Nitric Oxide Synthase Type II, Hepatocytes/physiology, S-Adenosylmethionine/analysis, Biology, Nitric Oxide, medicine, Animals, Rats, Wistar, Cells, Cultured, Hepatology, Hepatocyte Growth Factor, Cell growth, Growth factor, Gastroenterology, Liver regeneration, Rats, Cell biology, Transcription Factor AP-1, AP-1 transcription factor, NG-Nitroarginine Methyl Ester, medicine.anatomical_structure, Biochemistry, Methionine Adenosyltransferase, Hepatocyte, Hepatocytes, Hepatocyte growth factor, Nitric Oxide Synthase, Cell Division, Nitric Oxide/physiology, medicine.drug, Transforming growth factor |
| الوصف: | Background & Aims: Liver regeneration is a fundamental response of this organ to injury. Hepatocyte proliferation is triggered by growth factors, such as hepatocyte growth factor. However, hepatocytes need to be primed to react to mitogenic signals. It is known that nitrous oxide (NO), generated after partial hepatectomy, plays an important role in hepatocyte growth. Nevertheless, the molecular mechanisms behind this priming event are not completely known. S-adenosylmethionine (AdoMet) synthesis by methionine adenosyltransferase is the first step in methionine metabolism, and NO regulates hepatocyte S-adenosylmethionine levels through specific inhibition of this enzyme. We have studied the modulation of hepatocyte growth factor–induced proliferation by NO through the regulation of S-adenosylmethionine levels. Methods: Studies were conducted in cultured rat hepatocytes isolated by collagenase perfusion, which triggers NO synthesis. Results: The mitogenic response to hepatocyte growth factor was blunted when inducible NO synthase was inhibited; this process was overcome by the addition of an NO donor. This effect was dependent on methionine concentration in culture medium and intracellular S-adenosylmethionine levels. Accordingly, we found that S-adenosylmethionine inhibits hepatocyte growth factor–induced cyclin D1 and D2 expression, activator protein 1 induction, and hepatocyte proliferation. Conclusions: Together our findings indicate that NO may switch hepatocytes into a hepatocyte growth factor–responsive state through the down-regulation of S-adenosylmethionine levels. GASTROENTEROLOGY 2002;122:1355-1363 |
| وصف الملف: | application/pdf |
| تدمد: | 0016-5085 |
| DOI: | 10.1053/gast.2002.33020 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c56acc302a19dabd5fe59530139eb414 https://doi.org/10.1053/gast.2002.33020 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c56acc302a19dabd5fe59530139eb414 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00165085 |
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| DOI: | 10.1053/gast.2002.33020 |