title: Actin cytoskeleton modulates ADMA-induced NF-kappaB nuclear translocation and ICAM-1 expression in endothelial cells.
abstract: BACKGROUND
  Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor, increases the activity of NF-κB (NF-κB) and then induces the expression of intercellular adhesion molecule-1 (ICAM-1). However, the mechanisms regulating ADMA-induced NF-κB activation are unknown. This study investigated the function of actin cytoskeleton for ADMA-induced NF-κB activation and ICAM-1 expression in endothelial cells.
  
  
  METHODS
  Human umbilical vein endothelial cells (HUVEC) were cultured and left untreated or challenged for 24 h with 100 µM ADMA in the absence and presence of 5 µM cytochalasin D (Cyt D), or 1 µM Jasplakinolide (Jas). The form of actin cytoskeleton, the translocation of NF-κB, NF-κB DNA binding activity, and the expression of ICAM-1 were determined.
  
  
  RESULTS
  ADMA increased the formation of stress fiber in endothelial cells, and Cyt D clearly induced destabilization of the actin filaments. Either stabilizing or destabilizing the actin cytoskeleton prevented ADMA-induced NF-κB activation. It also showed that the inhibition of NF-κB activity was due to the impaired NF-κB nuclear translocation. Further, stabilizing or destabilizing the actin cytoskeleton inhibited the expression of the NF-κB target protein, ICAM-1.
  
  
  CONCLUSIONS
  Actin cytoskeleton may be engaged in modulated ADMA-induced NF-κB activation and thereby ICAM-1 expression in endothelial cells.
authors.affiliation: Department of Nephrology, Affiliated Beijing Friendship Hospital, Faculty of Kidney Diseases, Capital Medical University, Beijing, Peoples Republic of China.
authors.forename: Guo
authors.initials: G
authors.lastname: Wei-Kang
authors.forename: Zhang
authors.initials: Z
authors.lastname: Dong-Liang
authors.forename: Wang
authors.initials: W
authors.lastname: Xin-Xin
authors.forename: Kong
authors.initials: K
authors.lastname: Wei
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhang
authors.initials: Z
authors.lastname: Qi-Dong
authors.forename: Liu
authors.initials: L
authors.lastname: Wen-Hu
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D015638:Cytochalasin D / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D047630:Depsipeptides / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D022502:Stress Fibers / Q000187:drug effects / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D047630:Depsipeptides; D016328:NF-kappa B; D051996:Transcription Factor RelA; C057531:jasplakinolide; D018799:Intercellular Adhesion Molecule-1; D015638:Cytochalasin D; C018524:N,N-dimethylarginine; D004247:DNA; D001120:Arginine