Involvement of MAPK/ERK1/2 pathway in microcystin-induced microfilament reorganization in HL7702 hepatocytes

J Toxicol Environ Health A. 2018;81(21):1135-1141. doi: 10.1080/15287394.2018.1532715. Epub 2018 Nov 13.

Abstract

Several studies previously demonstrated that microcystin (MC)-LR produced cytoskeletal damage, especially to actin filaments. However, the underlying mechanisms of MC-induced cytoskeletal reorganization remain to be determined. The aim of this study was to examine the effects of 5 or 10 µM MC-LR on microfilament depolarization and expression of microRNA-451a (miR-451a) which plays a crucial role in cellular processes including cell proliferation, apoptosis and tumorigenesis in HL7702 liver cells after 24 hr treatment. Data demonstrated that MC-LR increased microfilament depolarization, elevated phosphorylation levels of mitogen-activated protein kinase (MAPK/ERK1/2) and vasodilator-stimulated phosphoprotein (VASP) but lowered miR-451a RNA expression levels. These molecular processes were associated with no marked changes in total protein ERK1/2. Data demonstrate that transfection with miR-451a may not be effective in the presence of MC-LR as evidenced by the inability of excess microRNA to prevent toxin-induced inhibition of threonine protein phosphatases1 (PP1) and 2A (PP2A) and microfilament reorganization in HL7702 cells.

Keywords: Hepatocytes; MAPK/ERK1/2; Microcystin-LR; Microfilament; Toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / drug effects
  • Actin Cytoskeleton / physiology*
  • Bacterial Toxins / toxicity*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Humans
  • Liver / drug effects*
  • Liver / metabolism
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology
  • Marine Toxins
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Microcystins / toxicity*
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Phosphorylation

Substances

  • Bacterial Toxins
  • Cell Adhesion Molecules
  • MIRN451 microRNA, human
  • Marine Toxins
  • MicroRNAs
  • Microcystins
  • Microfilament Proteins
  • Phosphoproteins
  • vasodilator-stimulated phosphoprotein
  • cyanoginosin LR