| Title | Myoglobin Induces Vascular Cell Adhesion Molecule-1 Expression through c-Src Kinase-Activator Protein-1/Nuclear Factor-kappaB Pathways. | | Author(s) | Kim SH, Chang JW, Kim SB, Park SK, Park JS, Lee SK | | Institution | Department of Internal Medicine, Asan Institute for Life Sciences, College of Medicine, University of Ulsan, Seoul, Korea. | | Source | Nephron Exp Nephrol 2009 Nov 3; 114(2):e48-e60. | | Abstract | Background/Aims: 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.
Methods: Activation of nuclear factor (NF)-kappaB 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.
Results: A sublethal dose of myoglobin (100 mug/ml) induced VCAM-1 expression via activation of AP-1 and NF-kappaB, which was mediated through activation of c-Src kinase, followed by mitogen-activated protein kinases (p38, ERK 1/2, JNK-1) and the IkappaB kinase - IkappaB-alpha. 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.
Conclusion: VCAM-1 expression via c-Src kinase-AP-1/NF-kappaB 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19887846 |
|
