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Dual role of endogenous nitric oxide in tumor necrosis factor shock: induced NO tempers oxidative stress

Anje Cauwels (UGent) , Jennyfer Bultinck (UGent) and Peter Brouckaert (UGent)
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Abstract
Tumor necrosis factor (TNF) is involved in pathologies like septic shock, inflammatory bowel disease and rheumatoid arthritis. TNF and lipopolysaccharide can incite lethal shock, in which cardiovascular collapse is centrally orchestrated by the vasodilating free radical nitric oxide (NO). However, NO synthase (NOS) inhibition causes increased morbidity and/or mortality, suggesting a dual role for NO. To investigate the potential protective role of NO during TNF shock, we treated mice with TNF with or without NOS inhibition. Experiments in endothelial-NOS- and inducible NOS-deficient mice identified inducible NOS as the source of protective NO. Distinctive TNF-induced lipid peroxidation, especially in liver and kidney, was aggravated by NOS inhibition. In addition, various antioxidant treatments and a phospholipase A2 (PLA2) inhibitor prevented sensitization by NOS inhibition. Together, these in vivo results indicate that induced NO not only causes hemodynamic collapse, but is also essential for curbing TNF-induced oxidative stress, which appears to hinge on PLA2-dependent mechanisms.
Keywords
TNF shock, mice, nitric oxide, oxidative stress, CYTOSOLIC PHOSPHOLIPASE A(2), SUPEROXIDE GENERATION, VASCULAR-RESISTANCE, LIPID-PEROXIDATION, INDUCED APOPTOSIS, SEPTIC SHOCK, FACTOR-ALPHA, KAPPA-B, SYNTHASE, INHIBITION

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Chicago
Cauwels, Anje, Jennyfer Bultinck, and Peter Brouckaert. 2005. “Dual Role of Endogenous Nitric Oxide in Tumor Necrosis Factor Shock: Induced NO Tempers Oxidative Stress.” Cmls-cellular and Molecular Life Sciences 62 (14): 1632–1640.
APA
Cauwels, Anje, Bultinck, J., & Brouckaert, P. (2005). Dual role of endogenous nitric oxide in tumor necrosis factor shock: induced NO tempers oxidative stress. CMLS-CELLULAR AND MOLECULAR LIFE SCIENCES, 62(14), 1632–1640.
Vancouver
1.
Cauwels A, Bultinck J, Brouckaert P. Dual role of endogenous nitric oxide in tumor necrosis factor shock: induced NO tempers oxidative stress. CMLS-CELLULAR AND MOLECULAR LIFE SCIENCES. 2005;62(14):1632–40.
MLA
Cauwels, Anje, Jennyfer Bultinck, and Peter Brouckaert. “Dual Role of Endogenous Nitric Oxide in Tumor Necrosis Factor Shock: Induced NO Tempers Oxidative Stress.” CMLS-CELLULAR AND MOLECULAR LIFE SCIENCES 62.14 (2005): 1632–1640. Print.
@article{322646,
  abstract     = {Tumor necrosis factor (TNF) is involved in pathologies like septic shock, inflammatory bowel disease and rheumatoid arthritis. TNF and lipopolysaccharide can incite lethal shock, in which cardiovascular collapse is centrally orchestrated by the vasodilating free radical nitric oxide (NO). However, NO synthase (NOS) inhibition causes increased morbidity and/or mortality, suggesting a dual role for NO. To investigate the potential protective role of NO during TNF shock, we treated mice with TNF with or without NOS inhibition. Experiments in endothelial-NOS- and inducible NOS-deficient mice identified inducible NOS as the source of protective NO. Distinctive TNF-induced lipid peroxidation, especially in liver and kidney, was aggravated by NOS inhibition. In addition, various antioxidant treatments and a phospholipase A2 (PLA2) inhibitor prevented sensitization by NOS inhibition. Together, these in vivo results indicate that induced NO not only causes hemodynamic collapse, but is also essential for curbing TNF-induced oxidative stress, which appears to hinge on PLA2-dependent mechanisms.},
  author       = {Cauwels, Anje and Bultinck, Jennyfer and Brouckaert, Peter},
  issn         = {1420-682X},
  journal      = {CMLS-CELLULAR AND MOLECULAR LIFE SCIENCES},
  keywords     = {TNF shock,mice,nitric oxide,oxidative stress,CYTOSOLIC PHOSPHOLIPASE A(2),SUPEROXIDE GENERATION,VASCULAR-RESISTANCE,LIPID-PEROXIDATION,INDUCED APOPTOSIS,SEPTIC SHOCK,FACTOR-ALPHA,KAPPA-B,SYNTHASE,INHIBITION},
  language     = {eng},
  number       = {14},
  pages        = {1632--1640},
  title        = {Dual role of endogenous nitric oxide in tumor necrosis factor shock: induced NO tempers oxidative stress},
  url          = {http://dx.doi.org/10.1007/s00018-005-5142-z},
  volume       = {62},
  year         = {2005},
}

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