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• W1979002012 abstract "<i>Background/Aims:</i> It is not clear whether a sublethal dose of myoglobin induces some pathophysiological changes in tubular cells, potentially affecting tubular injury or tubular regeneration. We investigated the effect of a low dose of myoglobin on vascular cell adhesion molecule-1 (VCAM-1) expression and elucidated the underlying signaling pathways. We further examined the effect of losartan and simvastatin on myoglobin-induced VCAM-1 expression and the signaling pathways. <i>Methods:</i> Activation of nuclear factor (NF)-ĸB and activator protein (AP)-1 was assessed by electrophoretic mobility shift assay. Phosphorylation of protein kinases was examined by Western blot analysis. VCAM-1 mRNA and protein were measured by Northern blot analysis and cell ELISA. <i>Results:</i> A sublethal dose of myoglobin (100 µg/ml) induced VCAM-1 expression via activation of AP-1 and NF-ĸB, which was mediated through activation of c-Src kinase, followed by mitogen-activated protein kinases (p38, ERK 1/2, JNK-1) and the IĸB kinase – IĸB-α. Inhibitors of protein kinase C and tyrosine kinase, antioxidants and intracellular calcium chelator suppressed myoglobin-induced activation of c-Src kinase. Losartan and simvastatin suppressed myoglobin-induced VCAM-1 expression via inhibition of c-Src kinase. <i>Conclusion:</i> VCAM-1 expression via c-Src kinase-AP-1/NF-ĸB pathways might be one of the possible mechanisms linking myoglobin to tubular injury. Losartan and simvastatin might be beneficial in attenuating myoglobin-induced tubular injury." @default.
• W1979002012 created "2016-06-24" @default.
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• W1979002012 date "2009-11-03" @default.
• W1979002012 modified "2023-09-25" @default.
• W1979002012 title "Myoglobin Induces Vascular Cell Adhesion Molecule-1 Expression through c-Src Kinase-Activator Protein-1/Nuclear Factor-ĸB Pathways" @default.
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• W1979002012 doi "https://doi.org/10.1159/000254391" @default.
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