title: NF-kappaB inhibitors significantly attenuate the transcription of high affinity type-2 cationic amino acid transporter in LPS-stimulated rat kidney.
abstract: BACKGROUND
  Sepsis-induced renal failure is closely related to inducible nitric oxide synthase (iNOS) upregulation and nitric oxide (NO) overproduction. Trans-membrane L-arginine transportation mediated by type-2 cationic amino acid transporter (CAT-2) isozymes, including CAT-2, CAT-2A, and CAT-2B, is one of the crucial mechanisms that regulate NO biosynthesis by iNOS. We previously had shown that endotoxemia significantly upregulated renal CAT-2 and CAT-2B but not CAT-2A expression. This study was, thus, conducted to further explore the role of nuclear factor-kappaB (NF-kappaB) in regulating the expression of CAT-2 isozymes in lipopolysaccharide (LPS)-treated rat kidney.
  
  
  METHODS
  Adult male Sprague-Dawley rats were randomly given intra-peritoneal injections of normal saline (N/S), LPS, LPS plus NF-kappaB inhibitor pre-treatment (PDTC, dexamethasone, or salicylate), or an NF-kappaB inhibitor alone. The rats were sacrificed at 6 hours after LPS injection and enzyme expression and renal injury were examined.
  
  
  RESULTS
  Renal iNOS, CAT-2, and CAT-2B were significantly upregulated in LPS-stimulated rat kidney. NF-kappa B inhibitors significantly attenuated this upregulation induced by LPS and resultantly attenuated renal NO biosynthesis and renal injury induced by LPS. In contrast, renal CAT-2A expression was not affected by either LPS or NF-kappaB inhibitors.
  
  
  CONCLUSIONS
  LPS co-induces iNOS, CAT-2 and CAT-2B expression in LPS-stimulated rat kidney. Furthermore, inhibition of NF-kappaB significantly attenuates NO biosynthesis through inhibition of iNOS, CAT-2, and CAT-2B, and, in turn, significantly reduces endotoxemia-induced renal injury.
authors.affiliation: Department of Anesthesiology, Mackay Memorial Hospital, Taipei, Taiwan, ROC.
authors.forename: Li-Chuan
authors.initials: LC
authors.lastname: Chu
authors.forename: Pei-Shan
authors.initials: PS
authors.lastname: Tsai
authors.forename: Jie-Jen
authors.initials: JJ
authors.lastname: Lee
authors.forename: Chia-Hsiang
authors.initials: CH
authors.lastname: Yen
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Huang
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001806:Blood Urea Nitrogen; D027202:Cationic Amino Acid Transporter 2 / Q000235:genetics*; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D027202:Cationic Amino Acid Transporter 2; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide