Lack of PPARα exacerbates lipopolysaccharide-induced liver toxicity through STAT1 inflammatory signaling and increased oxidative/nitrosative stress

Seong Ho Yoo, Ogyi Park, Lauren E. Henderson, Mohamed A. Abdelmegeed, Kwan Hoon Moon, Byoung Joon Song

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)23-29
Number of pages7
JournalToxicology Letters
Volume202
Issue number1
DOIs
StatePublished - Apr 10 2011
Externally publishedYes

Fingerprint

Peroxisome Proliferator-Activated Receptors
Oxidative stress
Liver
Toxicity
Lipopolysaccharides
Oxidative Stress
STAT Transcription Factors
Nitration
Wounds and Injuries
Oxidants
Lipid Peroxidation
Anti-Inflammatory Agents
Cytokines
Lipids
Enzymes
Proteins

Keywords

  • Acute liver damage
  • Cytokines
  • Lipopolysaccharide
  • Oxidative/nitrosative stress
  • PPARα
  • STAT

ASJC Scopus subject areas

  • Toxicology

Cite this

Lack of PPARα exacerbates lipopolysaccharide-induced liver toxicity through STAT1 inflammatory signaling and increased oxidative/nitrosative stress. / Yoo, Seong Ho; Park, Ogyi; Henderson, Lauren E.; Abdelmegeed, Mohamed A.; Moon, Kwan Hoon; Song, Byoung Joon.

In: Toxicology Letters, Vol. 202, No. 1, 10.04.2011, p. 23-29.

Research output: Contribution to journalArticle

Yoo, Seong Ho ; Park, Ogyi ; Henderson, Lauren E. ; Abdelmegeed, Mohamed A. ; Moon, Kwan Hoon ; Song, Byoung Joon. / Lack of PPARα exacerbates lipopolysaccharide-induced liver toxicity through STAT1 inflammatory signaling and increased oxidative/nitrosative stress. In: Toxicology Letters. 2011 ; Vol. 202, No. 1. pp. 23-29.
@article{8831f029cda84580bb34a256baa3878e,
title = "Lack of PPARα exacerbates lipopolysaccharide-induced liver toxicity through STAT1 inflammatory signaling and increased oxidative/nitrosative stress",
abstract = "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.",
keywords = "Acute liver damage, Cytokines, Lipopolysaccharide, Oxidative/nitrosative stress, PPARα, STAT",
author = "Yoo, {Seong Ho} and Ogyi Park and Henderson, {Lauren E.} and Abdelmegeed, {Mohamed A.} and Moon, {Kwan Hoon} and Song, {Byoung Joon}",
year = "2011",
month = "4",
day = "10",
doi = "10.1016/j.toxlet.2011.01.013",
language = "English (US)",
volume = "202",
pages = "23--29",
journal = "Toxicology Letters",
issn = "0378-4274",
publisher = "Elsevier BV",
number = "1",

}

TY - JOUR

T1 - Lack of PPARα exacerbates lipopolysaccharide-induced liver toxicity through STAT1 inflammatory signaling and increased oxidative/nitrosative stress

AU - Yoo, Seong Ho

AU - Park, Ogyi

AU - Henderson, Lauren E.

AU - Abdelmegeed, Mohamed A.

AU - Moon, Kwan Hoon

AU - Song, Byoung Joon

PY - 2011/4/10

Y1 - 2011/4/10

N2 - 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.

AB - 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.

KW - Acute liver damage

KW - Cytokines

KW - Lipopolysaccharide

KW - Oxidative/nitrosative stress

KW - PPARα

KW - STAT

UR - http://www.scopus.com/inward/record.url?scp=79952036436&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952036436&partnerID=8YFLogxK

U2 - 10.1016/j.toxlet.2011.01.013

DO - 10.1016/j.toxlet.2011.01.013

M3 - Article

VL - 202

SP - 23

EP - 29

JO - Toxicology Letters

JF - Toxicology Letters

SN - 0378-4274

IS - 1

ER -