title: Nuclear Receptor PPARα Agonist Wy-14,643 Ameliorates Hepatic Cell Death in Hepatic IKKβ-Deficient Mice.
abstract: Inhibitor of nuclear factor kappa-B kinase beta (IKKβ) plays a critical role in cell proliferation and inflammation in various cells by activating NF-κB signaling. However, the interrelationship between peroxisome proliferator-activated receptor α (PPARα) and IKKβ in cell proliferation is not clear. In this study, we investigated the possible role of PPARα in the hepatic cell death in the absence ofIKKβgene using liver-specificIkkb-null (IkkbF/F-AlbCre) mice. To examine the function of PPARα activation in hepatic cell death, wild-type (IkkbF/F) andIkkbF/F-AlbCremice were treated with PPARα agonist Wy-14,643 (0.1% w/w chow diet) for two weeks. As a result of Wy-14,643 treatment, apoptotic markers including caspase-3 cleavage, poly (ADP-ribose) polymerase (PARP) cleavage and TUNEL-positive staining were significantly decreased in theIkkbF/F-AlbCremice. Surprisingly, Wy-14,643 increased the phosphorylation of p65 and STAT3 in bothIkkbandIkkbF/F-AlbCremice. Furthermore, BrdU-positive cells were significantly increased in both groups after treatment with Wy-14,643. Our results suggested that IKKβ-derived hepatic apoptosis could be altered by PPARα activation in conjunction with activation of NF-κB and STAT3 signaling.
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Taehyeong
authors.initials: T
authors.lastname: Kim
authors.affiliation: Department of Pharmacology and Graduate School of Convergence Medical Science, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Republic of Korea.
authors.forename: Lilik Duwi
authors.initials: LD
authors.lastname: Wahyudi
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.|Department of Pharmacology and Graduate School of Convergence Medical Science, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Republic of Korea.
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Kim
keywords: IKKb; NF-kB; PPARa; STAT3; Wy-14,643