title: Fatty acid-bearing albumin induces VCAM-1 expression through c-Src kinase-AP-1/NF-kB 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-kappaB 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-kappaB, which was mediated through activation of c-Src kinase, followed by MAP kinases (p38, ERK 1/2, JNK-1) and IkappaB kinase and IkappaB-alpha, 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/NFkappaB 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.
authors.affiliation: Department of Internal Medicine, Asan Institute for Life Sciences, College of Medicine, University of Ulsan, Seoul, Korea.
authors.forename: Joo Eun
authors.initials: JE
authors.lastname: Baek
authors.forename: Won Suk
authors.initials: WS
authors.lastname: Yang
authors.forename: Jai Won
authors.initials: JW
authors.lastname: Chang
authors.forename: Soon Bae
authors.initials: SB
authors.lastname: Kim
authors.forename: Su Kil
authors.initials: SK
authors.lastname: Park
authors.forename: Jung Sik
authors.initials: JS
authors.lastname: Park
authors.forename: Sang Koo
authors.initials: SK
authors.lastname: Lee
mesh_terms: D000418:Albumins / Q000378:metabolism / Q000494:pharmacology; D000081247:CSK Tyrosine-Protein Kinase; D002331:Carnitine / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007674:Kidney Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000502:physiology*; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics*; D014803:Vitamin B Complex / Q000378:metabolism / Q000494:pharmacology; D019061:src-Family Kinases
chemical_list: D000418:Albumins; D005227:Fatty Acids; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D019010:Vascular Cell Adhesion Molecule-1; D014803:Vitamin B Complex; D000072000:NF-KappaB Inhibitor alpha; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D002331:Carnitine