Lack of PPARα exacerbates lipopolysaccharide-induced liver toxicity through STAT1 inflammatory signaling and increased oxidative/nitrosative stress
Open accessAbstract
Peroxisome proliferator-activated receptor-α (PPARα) has been implicated in a potent anti-inflammatory activity. However, no information is available on whether PPARα can affect signal transducers and activator of transcription proteins (STATs) in acute liver damage. Thus, this study was aimed to investigate the in vivo role of PPARα in elevating STATs as well as oxidative/nitrosative stress in a model of lipopolysaccharide (LPS)-induced acute hepatic inflammatory injury. Using age-matched Ppara-null and wild-type (WT) mice, we demonstrate that the deletion of PPARα aggravates LPS-mediated liver injury through activating STAT1 and NF-κB-p65 accompanied by increased levels of pro-inflammatory cytokines. Furthermore, the activities of key anti-oxidant enzymes and mitochondrial complexes were significantly decreased while lipid peroxidation and protein nitration were elevated in LPS-exposed Ppara-null mice compared to WT. These results indicate that PPARα is important in preventing LPS-induced acute liver damage by regulating STAT1 inflammatory signaling pathways and oxidative/nitrosative stress.
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Based on our results, similar results of mitochondrial dysfunction and tissue injury are expected with other conditions such as I/R injury and LPS treatment, which caused extensive protein nitration.
“Based on our results, we expect similar results of mitochondrial dysfunction and tissue injury with other conditions such as I/R injury [38] and LPS treatment [96], which caused extensive protein nitration.”
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- Authors
- Yoo, S. H., Park, O., Henderson, L. E., Abdelmegeed, M. A., Moon, K.-H., & Song, B.-J.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Song, Byoung-Joon
- Venue
- Toxicology Letters
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 202
- Issue
- 1
- Pages
- 23-29
- ISSN
- 0378-4274 (ISSN-L)
- PMC
- PMC3056153
- OpenAlex
- W2024951688
- Cited by
- 30
- References
- 34
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 4 · 2016: 2 · 2015: 2 · 2014: 4 · 2013: 4 · 2012: 1
- FWCI
- 1.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Toxicology Letters (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99‐AA999999)
- National Institute on Alcohol Abuse and Alcoholism (ZIAAA000036)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- PPARα, lipopolysaccharide, acute liver injury, STAT1, NF-κB, oxidative stress, nitrosative stress, inflammatory cytokines, lipid peroxidation, protein nitration, mitochondrial dysfunction, anti-inflammatory signaling
- MeSH terms
- Animals, Female, Lipopolysaccharides, Liver, Male, Malondialdehyde, Signal Transduction, Nitrosation, Cytokines, Oxidative Stress, PPAR alpha, STAT1 Transcription Factor, STAT3 Transcription Factor, Mice
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