Differential regulation of nitric oxide synthase isoforms in experimental acute Chagasic cardiomyopathy

B. Chandrasekar, Peter Melby, D. A. Troyer, G. L. Freeman

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

We have previously demonstrated induction and high level expression of IL-1β, IL-6 and tumour necrosis factor-alpha in the myocardium during the acute stage of experimental Trypanosoma cruzi infection (Chagas' disease). The myocardial depressive effects of these cytokines are mediated in part by the induction of nitric oxide synthase (NOS), production of nitric oxide (NO) and formation of peroxynitrite. In this study we investigated the expression, activity and localization of NOS isoforms, and the levels of NO, malondialdehyde (a measure of oxidative stress), and peroxynitrite in rats at 1.5, 5, 10 and 15 days after infection with T. cruzi trypomastigotes. The myocardial inflammatory infiltrate and number of amastigote nests increased over the course of infection. A significant increase in tissue nitrate + nitrite levels, NOS2 mRNA, and NOS2 enzyme activity was observed at all time points in the infected compared with uninfected animals. The enzyme activity of constitutive NOS, tissue malondialdehyde levels, and NOS3 mRNA levels was only transiently increased after infection. The protein levels of the NOS isoforms paralleled their mRNA expression. While no positive nitrotyrosine immunoreactivity was detected in control myocardium, its levels increased in infected animals over time. Thus, by 1.5 days post-infection, when no parasite or immune cell infiltration could be detected, the myocardium expressed high levels of NOS and NO metabolites. Nevertheless, the early production of NO in the myocardium was not sufficient to clear the parasites.

Original languageEnglish (US)
Pages (from-to)112-119
Number of pages8
JournalClinical and Experimental Immunology
Volume121
Issue number1
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Cardiomyopathies
Nitric Oxide Synthase
Protein Isoforms
Myocardium
Nitric Oxide
Infection
Peroxynitrous Acid
Trypanosoma cruzi
Malondialdehyde
Messenger RNA
Parasites
Chagas Disease
Enzymes
Nitrites
Interleukin-1
Nitrates
Interleukin-6
Oxidative Stress
Tumor Necrosis Factor-alpha
Cytokines

Keywords

  • Cardiomyopathy
  • Chagas' disease
  • Nitric oxide synthase
  • Peroxynitrite
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Immunology

Cite this

Differential regulation of nitric oxide synthase isoforms in experimental acute Chagasic cardiomyopathy. / Chandrasekar, B.; Melby, Peter; Troyer, D. A.; Freeman, G. L.

In: Clinical and Experimental Immunology, Vol. 121, No. 1, 2000, p. 112-119.

Research output: Contribution to journalArticle

@article{7876413a588b463493bb71315154260a,
title = "Differential regulation of nitric oxide synthase isoforms in experimental acute Chagasic cardiomyopathy",
abstract = "We have previously demonstrated induction and high level expression of IL-1β, IL-6 and tumour necrosis factor-alpha in the myocardium during the acute stage of experimental Trypanosoma cruzi infection (Chagas' disease). The myocardial depressive effects of these cytokines are mediated in part by the induction of nitric oxide synthase (NOS), production of nitric oxide (NO) and formation of peroxynitrite. In this study we investigated the expression, activity and localization of NOS isoforms, and the levels of NO, malondialdehyde (a measure of oxidative stress), and peroxynitrite in rats at 1.5, 5, 10 and 15 days after infection with T. cruzi trypomastigotes. The myocardial inflammatory infiltrate and number of amastigote nests increased over the course of infection. A significant increase in tissue nitrate + nitrite levels, NOS2 mRNA, and NOS2 enzyme activity was observed at all time points in the infected compared with uninfected animals. The enzyme activity of constitutive NOS, tissue malondialdehyde levels, and NOS3 mRNA levels was only transiently increased after infection. The protein levels of the NOS isoforms paralleled their mRNA expression. While no positive nitrotyrosine immunoreactivity was detected in control myocardium, its levels increased in infected animals over time. Thus, by 1.5 days post-infection, when no parasite or immune cell infiltration could be detected, the myocardium expressed high levels of NOS and NO metabolites. Nevertheless, the early production of NO in the myocardium was not sufficient to clear the parasites.",
keywords = "Cardiomyopathy, Chagas' disease, Nitric oxide synthase, Peroxynitrite, Trypanosoma cruzi",
author = "B. Chandrasekar and Peter Melby and Troyer, {D. A.} and Freeman, {G. L.}",
year = "2000",
doi = "10.1046/j.1365-2249.2000.01258.x",
language = "English (US)",
volume = "121",
pages = "112--119",
journal = "Clinical and Experimental Immunology",
issn = "0009-9104",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Differential regulation of nitric oxide synthase isoforms in experimental acute Chagasic cardiomyopathy

AU - Chandrasekar, B.

AU - Melby, Peter

AU - Troyer, D. A.

AU - Freeman, G. L.

PY - 2000

Y1 - 2000

N2 - We have previously demonstrated induction and high level expression of IL-1β, IL-6 and tumour necrosis factor-alpha in the myocardium during the acute stage of experimental Trypanosoma cruzi infection (Chagas' disease). The myocardial depressive effects of these cytokines are mediated in part by the induction of nitric oxide synthase (NOS), production of nitric oxide (NO) and formation of peroxynitrite. In this study we investigated the expression, activity and localization of NOS isoforms, and the levels of NO, malondialdehyde (a measure of oxidative stress), and peroxynitrite in rats at 1.5, 5, 10 and 15 days after infection with T. cruzi trypomastigotes. The myocardial inflammatory infiltrate and number of amastigote nests increased over the course of infection. A significant increase in tissue nitrate + nitrite levels, NOS2 mRNA, and NOS2 enzyme activity was observed at all time points in the infected compared with uninfected animals. The enzyme activity of constitutive NOS, tissue malondialdehyde levels, and NOS3 mRNA levels was only transiently increased after infection. The protein levels of the NOS isoforms paralleled their mRNA expression. While no positive nitrotyrosine immunoreactivity was detected in control myocardium, its levels increased in infected animals over time. Thus, by 1.5 days post-infection, when no parasite or immune cell infiltration could be detected, the myocardium expressed high levels of NOS and NO metabolites. Nevertheless, the early production of NO in the myocardium was not sufficient to clear the parasites.

AB - We have previously demonstrated induction and high level expression of IL-1β, IL-6 and tumour necrosis factor-alpha in the myocardium during the acute stage of experimental Trypanosoma cruzi infection (Chagas' disease). The myocardial depressive effects of these cytokines are mediated in part by the induction of nitric oxide synthase (NOS), production of nitric oxide (NO) and formation of peroxynitrite. In this study we investigated the expression, activity and localization of NOS isoforms, and the levels of NO, malondialdehyde (a measure of oxidative stress), and peroxynitrite in rats at 1.5, 5, 10 and 15 days after infection with T. cruzi trypomastigotes. The myocardial inflammatory infiltrate and number of amastigote nests increased over the course of infection. A significant increase in tissue nitrate + nitrite levels, NOS2 mRNA, and NOS2 enzyme activity was observed at all time points in the infected compared with uninfected animals. The enzyme activity of constitutive NOS, tissue malondialdehyde levels, and NOS3 mRNA levels was only transiently increased after infection. The protein levels of the NOS isoforms paralleled their mRNA expression. While no positive nitrotyrosine immunoreactivity was detected in control myocardium, its levels increased in infected animals over time. Thus, by 1.5 days post-infection, when no parasite or immune cell infiltration could be detected, the myocardium expressed high levels of NOS and NO metabolites. Nevertheless, the early production of NO in the myocardium was not sufficient to clear the parasites.

KW - Cardiomyopathy

KW - Chagas' disease

KW - Nitric oxide synthase

KW - Peroxynitrite

KW - Trypanosoma cruzi

UR - http://www.scopus.com/inward/record.url?scp=0033916962&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033916962&partnerID=8YFLogxK

U2 - 10.1046/j.1365-2249.2000.01258.x

DO - 10.1046/j.1365-2249.2000.01258.x

M3 - Article

VL - 121

SP - 112

EP - 119

JO - Clinical and Experimental Immunology

JF - Clinical and Experimental Immunology

SN - 0009-9104

IS - 1

ER -