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

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Nitric Oxide Synthase
Lipopolysaccharides
Lung
Nitric Oxide
Lung Injury
Isoenzymes
Cationic Amino Acid Transporter 2
Arginine
Enzyme Induction
Endotoxemia
Salicylates
Nitric Oxide Synthase Type II
Intravenous Injections
Dexamethasone
Sprague Dawley Rats
Injections
Membranes
Enzymes

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

Cite this

NF-kappaB involvement in the induction of high affinity CAT-2 in lipopolysaccharide-stimulated rat lungs. / Huang, CJ; Tsai, Pei-Shan; Lu, YT; Cheng, CR; Stevens, BR; Skimming, JW; Pan, WH.

In: Acta Anaesthesiologica Scandinavica, Vol. 48, No. 8, 09.2004, p. 992-1002.

Research output: Contribution to journalArticle

Huang, CJ ; Tsai, Pei-Shan ; Lu, YT ; Cheng, CR ; Stevens, BR ; Skimming, JW ; Pan, WH. / NF-kappaB involvement in the induction of high affinity CAT-2 in lipopolysaccharide-stimulated rat lungs. In: Acta Anaesthesiologica Scandinavica. 2004 ; Vol. 48, No. 8. pp. 992-1002.
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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.",
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AU - Huang, CJ

AU - Tsai, Pei-Shan

AU - Lu, YT

AU - Cheng, CR

AU - Stevens, BR

AU - Skimming, JW

AU - Pan, WH

PY - 2004/9

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N2 - 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.

AB - 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.

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KW - Hemodynamics

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KW - Male

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KW - Nitric Oxide

KW - Nitric Oxide Synthase

KW - Nitric Oxide Synthase Type II

KW - Organ Size

KW - Peroxidase

KW - RNA, Messenger

KW - Rats

KW - Rats, Sprague-Dawley

KW - Respiration, Artificial

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Stimulation, Chemical

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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U2 - 10.1111/j.1399-6576.2004.00454.x

DO - 10.1111/j.1399-6576.2004.00454.x

M3 - Article

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VL - 48

SP - 992

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JO - Acta Anaesthesiologica Scandinavica

JF - Acta Anaesthesiologica Scandinavica

SN - 0001-5172

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