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[The pattern of nuclear factor-kappaB activation in rats with endotoxin shock and its role in biopterin-mediated nitric oxide induction].
Zhonghua Shao Shang Za Zhi. 2006 Dec; 22(6):405-10.ZS

Abstract

OBJECTIVE

To investigate the pattern of nuclear factor-kappaB (NF-kappaB) activation in rats with lipopolysaccharide(LPS) shock, and to explore the mechanism of NF-kappaB signal pathway in the biopterin-mediated nitric oxide(NO) induction, as well as its role in the development of multiple organ dysfunction syndrome (MODS) secondary to endotoxin challenge.

METHODS

Fourty-seven male Wistar rats were randomly divided into control group (C, n = 8) , LPS group (n = 24, with 8 rats at each time-points, and shock model was made by injection of same dosage of LPS) , and pyrrolidine dithiocarbamate (PDTC) treatment group (PDTC, n = 15, with 5 rats at each time-points, and the rats were injected with LPS and PDTC). The rats were sacrificed at 2,6,12 post-injection hour(PIH) , and the blood and tissue samples from liver, lungs and kidneys were harvested for the determination of NF-KB activity, GTP cyclohydrolase I (GTP-CH I) , and inducible nitric oxide synthase (iNOS) mRNA expression in the liver, lungs and kidneys, plasma and tissue content of biopterin and NO, as well as hepatic and renal function, and pulmonary myeloperoxidase activity.

RESULTS

NF-kappaB DNA binding activity in LPS group was rapidly enhanced in liver, lungs and kidneys after endotoxin challenge when compared with that in controls (e. g. in pulmonary tissue it was 26+/-6) , and it reached the peak at 2 PIH, which was 291 +/-44 in pulmonary tissue(P <0. 01). GTP-CH I mRNA expression and biopterin levels in the liver, lung and kidney of each group were obviously higher than those in control group(P <0.05 or 0.01) , and it maintained at high levels at 12 PIH. Additionally, different degrees of dysfunction of the above mentioned organs was observed. Treatment with PDTC, an inhibitor of NF-KB signal transduction pathway, could reduce NF-kappaB DNA binding activity, inhibit GTP-CH I and iNOS/NO mRNA expression, as well as BH4, and NO levels in various tissues. Meanwhile the multiple organ damage was significantly ameliorated by PDTC pretreatment.

CONCLUSION

Endotoxin challenge can rapidly lead to activation of NF-kappaB in various tissues, and NF-KB pathway might markedly up-regulate the production of biopterin/NO following endotoxic shock. Inhibition of NF-kappaB pathway attenuates inflammatory response and ameliorates multiple organ dysfunction, which might be associated with its down-regulation of the excessive activation of iNOS mediated by biopterin.

Authors+Show Affiliations

Burn Institute, First Hospital Affiliated to the PLA General Hospital, Beijing, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

English Abstract
Journal Article
Research Support, Non-U.S. Gov't

Language

chi

PubMed ID

17438682

Citation

Yao, Yong-ming, et al. "[The Pattern of Nuclear factor-kappaB Activation in Rats With Endotoxin Shock and Its Role in Biopterin-mediated Nitric Oxide Induction]." Zhonghua Shao Shang Za Zhi = Zhonghua Shaoshang Zazhi = Chinese Journal of Burns, vol. 22, no. 6, 2006, pp. 405-10.
Yao YM, Xu CL, Yao FH, et al. [The pattern of nuclear factor-kappaB activation in rats with endotoxin shock and its role in biopterin-mediated nitric oxide induction]. Zhonghua Shao Shang Za Zhi. 2006;22(6):405-10.
Yao, Y. M., Xu, C. L., Yao, F. H., Yu, Y., & Sheng, Z. Y. (2006). [The pattern of nuclear factor-kappaB activation in rats with endotoxin shock and its role in biopterin-mediated nitric oxide induction]. Zhonghua Shao Shang Za Zhi = Zhonghua Shaoshang Zazhi = Chinese Journal of Burns, 22(6), 405-10.
Yao YM, et al. [The Pattern of Nuclear factor-kappaB Activation in Rats With Endotoxin Shock and Its Role in Biopterin-mediated Nitric Oxide Induction]. Zhonghua Shao Shang Za Zhi. 2006;22(6):405-10. PubMed PMID: 17438682.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [The pattern of nuclear factor-kappaB activation in rats with endotoxin shock and its role in biopterin-mediated nitric oxide induction]. AU - Yao,Yong-ming, AU - Xu,Cai-lin, AU - Yao,Feng-hua, AU - Yu,Yan, AU - Sheng,Zhi-yong, PY - 2007/4/19/pubmed PY - 2009/6/12/medline PY - 2007/4/19/entrez SP - 405 EP - 10 JF - Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi = Chinese journal of burns JO - Zhonghua Shao Shang Za Zhi VL - 22 IS - 6 N2 - OBJECTIVE: To investigate the pattern of nuclear factor-kappaB (NF-kappaB) activation in rats with lipopolysaccharide(LPS) shock, and to explore the mechanism of NF-kappaB signal pathway in the biopterin-mediated nitric oxide(NO) induction, as well as its role in the development of multiple organ dysfunction syndrome (MODS) secondary to endotoxin challenge. METHODS: Fourty-seven male Wistar rats were randomly divided into control group (C, n = 8) , LPS group (n = 24, with 8 rats at each time-points, and shock model was made by injection of same dosage of LPS) , and pyrrolidine dithiocarbamate (PDTC) treatment group (PDTC, n = 15, with 5 rats at each time-points, and the rats were injected with LPS and PDTC). The rats were sacrificed at 2,6,12 post-injection hour(PIH) , and the blood and tissue samples from liver, lungs and kidneys were harvested for the determination of NF-KB activity, GTP cyclohydrolase I (GTP-CH I) , and inducible nitric oxide synthase (iNOS) mRNA expression in the liver, lungs and kidneys, plasma and tissue content of biopterin and NO, as well as hepatic and renal function, and pulmonary myeloperoxidase activity. RESULTS: NF-kappaB DNA binding activity in LPS group was rapidly enhanced in liver, lungs and kidneys after endotoxin challenge when compared with that in controls (e. g. in pulmonary tissue it was 26+/-6) , and it reached the peak at 2 PIH, which was 291 +/-44 in pulmonary tissue(P <0. 01). GTP-CH I mRNA expression and biopterin levels in the liver, lung and kidney of each group were obviously higher than those in control group(P <0.05 or 0.01) , and it maintained at high levels at 12 PIH. Additionally, different degrees of dysfunction of the above mentioned organs was observed. Treatment with PDTC, an inhibitor of NF-KB signal transduction pathway, could reduce NF-kappaB DNA binding activity, inhibit GTP-CH I and iNOS/NO mRNA expression, as well as BH4, and NO levels in various tissues. Meanwhile the multiple organ damage was significantly ameliorated by PDTC pretreatment. CONCLUSION: Endotoxin challenge can rapidly lead to activation of NF-kappaB in various tissues, and NF-KB pathway might markedly up-regulate the production of biopterin/NO following endotoxic shock. Inhibition of NF-kappaB pathway attenuates inflammatory response and ameliorates multiple organ dysfunction, which might be associated with its down-regulation of the excessive activation of iNOS mediated by biopterin. SN - 1009-2587 UR - https://www.unboundmedicine.com/medline/citation/17438682/[The_pattern_of_nuclear_factor_kappaB_activation_in_rats_with_endotoxin_shock_and_its_role_in_biopterin_mediated_nitric_oxide_induction]_ L2 - http://journal.yiigle.com/LinkIn.do?linkin_type=pubmed&amp;issn=1009-2587&amp;year=2006&amp;vol=22&amp;issue=6&amp;fpage=405 DB - PRIME DP - Unbound Medicine ER -