Relationship between peroxisome proliferator-activated receptor alpha activity and cellular concentration of 14 perfluoroalkyl substances in HepG2 cells

2017 ◽  
Vol 38 (2) ◽  
pp. 219-226 ◽  
Author(s):  
Anna Kjerstine Rosenmai ◽  
Lutz Ahrens ◽  
Théo le Godec ◽  
Johan Lundqvist ◽  
Agneta Oskarsson
Keyword(s):  
Hepg2 Cells ◽  
Alpha Activity ◽  
Perfluoroalkyl Substances ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Alpha ◽  
Cellular Concentration

scholarly journals Pro-inflammatory signaling by 24,25-dihydroxyvitamin D3 in HepG2 cells

2016 ◽  
Vol 57 (2) ◽  
pp. 87-96 ◽  
Author(s):  
Kent Wehmeier ◽  
Luisa M Onstead-Haas ◽  
Norman C W Wong ◽  
Arshag D Mooradian ◽  
Michael J Haas
Keyword(s):  
Vitamin D ◽  
Signaling Pathways ◽  
Hepg2 Cells ◽  
Density Lipoprotein ◽  
Hepatic Function ◽  
Peroxisome Proliferator ◽  
Dihydroxyvitamin D3 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Alpha ◽  
Hydroxyvitamin D

The vitamin D metabolite 24,25-dihydroxyvitamin D3(24, 25[OH]2D3) was shown to induce nongenomic signaling pathways in resting zone chondrocytes and other cells involved in bone remodeling. Recently, our laboratory demonstrated that 24,25-[OH]2D3but not 25-hydroxyvitamin D3, suppresses apolipoprotein A-I (apo A-I) gene expression and high-density lipoprotein (HDL) secretion in hepatocytes. Since 24,25-[OH]2D3has low affinity for the vitamin D receptor (VDR) and little is known with regard to how 24,25-[OH]2D3modulates nongenomic signaling in hepatocytes, we investigated the capacity of 24,25-[OH]2D3to activate various signaling pathways relevant to apo A-I synthesis in HepG2 cells. Treatment with 24,25-[OH]2D3resulted in decreased peroxisome proliferator-activated receptor alpha (PPARα) expression and retinoid-X-receptor alpha (RXRα) expression. Similarly, treatment of hepatocytes with 50 nM 24,25-[OH]2D3for 1–3 h induced PKCα activation as well as c-jun-N-terminal kinase 1 (JNK1) activity and extracellular-regulated kinase 1/2 (ERK1/2) activity. These changes in kinase activity correlated with changes in c-junphosphorylation, an increase in AP-1-dependent transcriptional activity, as well as repression of apo A-I promoter activity. Furthermore, treatment with 24,25-[OH]2D3increased IL-1β, IL-6, and IL-8 expression by HepG2 cells. These observations suggest that 24,25-[OH]2D3elicits several novel rapid nongenomic-mediated pro-inflammatory protein kinases targeting AP1 activity, increasing pro-inflammatory cytokine expression, potentially impacting lipid metabolism and hepatic function.

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