1,3-dichloro-2-propanol induced lipid accumulation in HepG2 cells through cAMP/protein kinase A and AMP-activated protein kinase pathways via Gi/o-coupled receptors

Environ Toxicol Pharmacol. 2017 Oct:55:118-126. doi: 10.1016/j.etap.2017.07.013. Epub 2017 Jul 27.

Abstract

1,3-dichloro-2-propanol (1,3-DCP) is a food born hepatoxic chloropropanol contaminant that has been detected in a wide range of foods. In the present study, we investigated the effects and mechanisms of 1,3-DCP on lipid accumulation in HepG2 cells. The data showed 1,3-DCP significantly increased intracellular content of triglyceride (TG) and total cholesterol (TC) at 0.5-2μg/mL. Further results showed that 1,3-DCP greatly decreased cyclic AMP (cAMP) level. In addition, 1,3-DCP inhibited PKA and AMPK signaling pathway, but had no influence on intracellular calcium and regulated proteins. Moreover, Gi/o protein inhibitor PTX significantly inhibited 1,3-DCP induced decrease of cAMP, p-PKA and p-AMPK expression. Furthermore, 1,3-DCP significantly decreased GPR41 and GPR43 expression, but had no effect on GPR109B.Thus, we concluded that 1,3-DCP induced lipid accumulation in HepG2 cells through cAMP/PKA and AMPK signaling pathways via Gi/o-coupled receptor.

Keywords: 1,3-DCP; AMPK; Gi/o; Lipid accumulation; PKA; cAMP.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Calcium / metabolism
  • Cholesterol / metabolism
  • Cyclic AMP / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Down-Regulation
  • Hep G2 Cells
  • Humans
  • Lipid Metabolism / drug effects*
  • Mutagens / toxicity*
  • Phosphorylation
  • Receptors, Cell Surface / metabolism
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Nicotinic / metabolism
  • Signal Transduction / drug effects*
  • Triglycerides / metabolism
  • alpha-Chlorohydrin / analogs & derivatives*
  • alpha-Chlorohydrin / toxicity

Substances

  • FFA2R protein, human
  • FFAR3 protein, human
  • HCAR3 protein, human
  • Mutagens
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Nicotinic
  • Triglycerides
  • 1,3-dichloro-2-propanol
  • alpha-Chlorohydrin
  • Cholesterol
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • AMP-Activated Protein Kinases
  • Calcium