High glucose induces transactivation of the alpha2-HS glycoprotein gene through the ERK1/2 signaling pathway. (65/175)

AIM: Alpha2-Heremans Schmid glycoprotein (AHSG), also known as fetuin-A, is secreted from the liver and inhibits tyrosine kinase activity of the insulin receptor. Hyperglycemia in type 2 diabetes is not only a secondary manifestation of insulin resistance, but could also be responsible for directly inducing insulin resistance in target tissues. In this study, we examined the effect of high glucose (HG) on AHSG gene transcription in the human hepatoma cell line HepG2. METHODS: AHSG transcriptional activity and protein expression were evaluated using reporter gene assays and Western blot analysis, respectively. RESULTS: D-glucose, but not L-glucose or mannitol, dose-dependently enhanced AHSG promoter activity. HG (25 mM) also increased AHSG protein expression. No protein kinase C inhibitors (bisindolylmaleimide, Ro-31-8220), an inhibitor of hexosamine biosynthesis pathway (6-diazo-5-oxo-L-norleucine), or a superoxide radical scavenger (tempol) affected HG-induced transactivation. MAPK/ERK kinase inhibitors (PD98059, U0126), but not the JNK inhibitor (SP600125) or p38 inhibitor (SB203580), significantly inhibited promoter activation by HG. CONCLUSION: Our data suggest that HG enhances AHSG transcription through activation of the ERK1/2 signaling pathway. Increased AHSG expression in the liver may be a cause of glucose toxicity in the diabetic state.  (+info)

Fetuin-A promotes primary keratinocyte migration: independent of epidermal growth factor receptor signalling. (66/175)

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Fetuin-A and change in body composition in older persons. (67/175)

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Association of lower plasma fetuin-a levels with peripheral arterial disease in type 2 diabetes. (68/175)

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Peripheral administration of fetuin-A attenuates early cerebral ischemic injury in rats. (69/175)

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Association of AHSG gene polymorphisms with fetuin-A plasma levels and cardiovascular diseases in the EPIC-Potsdam study. (70/175)

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Pseudoxanthoma elasticum: molecular genetics and putative pathomechanisms. (71/175)

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Fetuin-A is an independent determinant of change of aortic stiffness over 1 year in non-diabetic patients with CKD stages 3 and 4. (72/175)

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