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Cited by 37NF-κB Signaling PathwaysClinical Nutrition and GastroenterologyImmune Response and Inflammation

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Supplementation of N-Acetylcysteine Normalizes Lipopolysaccharide-Induced Nuclear Factor κB Activation and Proinflammatory Cytokine Production During Early Rehabilitation of Protein Malnourished Mice

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Li, Jun, Quan, Ning, Bray, Tammy M.·2002·The Journal of Nutrition
DOI 10.1093/jn/132.11.3286
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Abstract

Increased sensitivity to septic shock has been reported in protein malnourished patients. In this study, we used an animal septic shock model to investigate effects of glutathione (GSH) levels on nuclear factor kappaB (NFkappaB) activation and proinflammatory cytokine production in protein malnutrition. We further investigated molecular mechanisms by which protein malnutrition influenced inflammatory responses. CD-1 mice were fed for 3 wk a normal protein (150 g/kg) diet or a protein-deficient (5 g/kg) diet, or for 2 wk a protein-deficient diet followed by 1 wk of N-acetylcysteine (NAC) supplementation. Lipopolysaccharide (LPS) was injected intravenously, and liver was collected at 0, 15 min, 1, 4, 24 and 48 h after LPS administration. Protein malnutrition significantly increased the activation of NFkappaB and transcription levels of its downstream genes interleukin-1beta and tumor necrosis factor-alpha. Peak NFkappaB activation was inversely associated with GSH levels (r = -0.939, P < 0.0001) but positively correlated with the GSH disulfide/2GSH reduction potential (r = 0.944 P < 0.0001). We noted unusual NFkappaB p50/p50 homodimer translocation that was significantly elevated in tissue from protein malnourished mice, along with decreased peak levels of normal p65/p50 heterodimer translocation. Interestingly, mRNA levels of IkappaB-alpha were not affected by protein malnutrition. However, early supplementation of NAC to protein malnourished mice without replenishing with dietary protein restored GSH levels and reduction potential, and normalized NFkappaB activation and proinflammatory cytokine production. Taken together, these findings provide evidence supporting the role of GSH in NFkappaB activation and inflammatory response in protein malnutrition, and the use of NAC in early rehabilitation of protein malnutrition without a high protein diet.

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  • The two other studies that found NFκB elevated in liver at 1 h post-LPS used gel shift analyses without subsequent supershift confirmation.

    “the other two investigations were performed using gel shift analyses without subsequent supershift confirmation to ensure that both subunits of prototypical NFκB were in the DNA-binding complex.”

    From Synthesis of IL-6 by Hepatocytes Is a Normal Response to Common Hepatic Stimuli (2014) · cites this paper as [15]

    The Methods section (‘NFκB nuclear translocation’; page unavailable) explicitly describes an EMSA supershift assay using antibodies to p50 or p65. The Results (‘NFκB subunit translocation’; page unavailable) report a supershift result at 15 minutes after LPS, contrary to the claim that this investigation used gel shifts without subsequent supershift confirmation. The copy does not show a supershift at the specific 1-hour time point. (LLM, conf=0.88)

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  • NFκB signaling occurs at 1 h after LPS injection in mice.

    “We also verified there was NFκB signaling at 1 h after LPS injection, when translocation of NFκB peaks after LPS administration in mice [15].”

    From Synthesis of IL-6 by Hepatocytes Is a Normal Response to Common Hepatic Stimuli (2014) · cites this paper as [15]

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Metadata

Authors
Li, J., Quan, N., & Bray, T. M.
Affiliations
The Ohio State University (US)
ORCID
Venue
The Journal of Nutrition
Publisher
Elsevier BV
Published
2002-11
Volume
132
Issue
11
Pages
3286-3292
ISSN
0022-3166 (ISSN-L)
DOI
10.1093/jn/132.11.3286
OpenAlex
W1950789953
Cited by
37
References
0
Citations by year
2025: 1 · 2023: 1 · 2019: 1 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 3
FWCI
1.44
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Nutrition (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (7r01ns038315-05)
  • National Institute of Neurological Disorders and Stroke (R01 NS38315)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
N-acetylcysteine, protein malnutrition, glutathione, NF-κB activation, lipopolysaccharide, septic shock, inflammatory cytokines, IL-1β, TNF-α, IκBα, liver inflammation, dietary protein deficiency, nutritional rehabilitation
MeSH terms
NF-KappaB Inhibitor alpha, Acetylcysteine, Animals, Biological Transport, Cell Nucleus, Chromatography, High Pressure Liquid, Glutathione, Interleukin-1, Lipopolysaccharides, Male, Oxidation-Reduction, Protein Deficiency, RNA, Messenger, Tumor Necrosis Factor-alpha, Cytokines, NF-kappa B, In Situ Hybridization, Dietary Supplements, I-kappa B Proteins, Mice

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