NF-kappaB involvement in the induction of high affinity CAT-2 in lipopolysaccharide-stimulated rat lungs

CJ Huang, Pei-Shan Tsai, YT Lu, CR Cheng, BR Stevens, JW Skimming, WH Pan

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

BACKGROUND: Endotoxemia stimulates nitric oxide (NO) biosynthesis through induction of inducible NO synthase (iNOS). Cellular uptake of L-arginine, the sole substrate for iNOS, is an important mechanism regulating NO biosynthesis by iNOS. The isozymes of type-2 cationic amino acid transporters, including CAT-2, CAT-2A, and CAT-2B, constitute the most important pathways responsible for trans-membrane L-arginine transportation. Therefore, regulation of CAT-2 isozymes expression may constitute one of the downstream regulatory pathways that control iNOS activity. We investigated the time course of enzyme induction and the role of nuclear factor-kappaB (NF-kappaB) in CAT-2 isozymes expression in lipopolysaccharide-(LPS) treated rat lungs.

METHODS: Adult male Sprague-Dawley rats were randomly given intravenous 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 different times after injection and enzyme expression and lung injury were examined. Pulmonary and systemic NO production were also measured.

RESULTS: LPS co-induced iNOS, CAT-2, and CAT-2B but not CAT-2A expression in the lungs. Furthermore, NF-kappaB actively participated in LPS-induction of iNOS, CAT-2, and CAT-2B. LPS induced pulmonary and systemic NO overproduction and resulted in lung injuries. Attenuation of LPS-induced iNOS, CAT-2, and CAT-2B induction significantly inhibited NO biosynthesis and lessened lung injury.

CONCLUSION: NF-kappaB actively participates in the induction of CAT-2 and CAT-2B in intact animals. Our data further support the idea that CAT-2 and CAT-2B are crucial in regulating iNOS activity.

Original languageEnglish
Pages (from-to)992-1002
Number of pages11
JournalActa Anaesthesiologica Scandinavica
Volume48
Issue number8
DOIs
Publication statusPublished - Sep 2004

Keywords

  • Animals
  • Cationic Amino Acid Transporter 2
  • Endotoxins
  • Hemodynamics
  • Lipopolysaccharides
  • Lung
  • Male
  • NF-kappa B
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Organ Size
  • Peroxidase
  • RNA, Messenger
  • Rats
  • Rats, Sprague-Dawley
  • Respiration, Artificial
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stimulation, Chemical
  • Journal Article
  • Research Support, Non-U.S. Gov't

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