Fatty Acid-Bearing Albumin Induces VCAM-1 Expression through c-Src Kinase-AP-1/NF-ĸB Pathways: Effect of L-Carnitine

Abstract

Background: Fatty acid-bearing albumin [FA(+) albumin] exerts more deleterious effects in tubular cells than albumin alone. We investigated the effect of FA(+) albumin on the vascular cell adhesion molecule-1 (VCAM-1) expression and elucidated the underlying signaling pathways. We further examined the effect of L-carnitine, since it was known to modulate intracellular fatty acid concentration. Methods: Activation of AP-1 and NF-ĸB was assessed by electrophoretic mobility shift assay. Phosphorylation of protein kinase was examined by Western blot analysis. VCAM-1 mRNA and protein expression were measured by Northern blot analysis and cell ELISA. Results: FA(+) albumin induced VCAM-1 expression via activation of AP-1 and NF-ĸB, which was mediated through activation of c-Src kinase, followed by MAP kinases (p38, ERK 1/2, JNK-1) and IĸB kinase and IĸB-α, respectively. Inhibitors of protein kinase C and tyrosine kinase, anti-oxidants and intracellular calcium chelator suppressed the FA(+) albumin-induced activation of c-Src kinase. L-Carnitine suppressed the FA(+) albumin-induced VCAM-1 expression via inhibition of c-Src kinase. Conclusions: VCAM-1 expression with activation of c-Src kinase-AP-1/NFĸB pathways might be one of the possible mechanisms that linked FA(+) albumin to tubulointerstitial injury. L-Carnitine might be beneficial in attenuating FA(+) albumin-induced tubular injury.