Manganese induces the overexpression of α-synuclein in PC12 cells via ERK activation

Brain Res. 2010 Nov 4;1359:201-7. doi: 10.1016/j.brainres.2010.08.055. Epub 2010 Aug 22.

Abstract

Manganese has been known to induce neurological disorders. In the present study, we determined the effect of manganese on the expression of α-synuclein in PC12 cells and its role in manganese-induced cytotoxicity. We also investigated the relationship between α-synuclein expression and the change of ERK1/2 MAPK activity. In our research, manganese exposure induced the overexpression of α-synuclein, while siRNA knockdown of α-synuclein reversed manganese-induced cytotoxicity. Furthermore, manganese induced the activation of ERK1/2 MAPK. The MEK1 inhibitor PD98059, which inhibits the activation of ERK MAPK, attenuated the overexpression of α-synuclein and the cytotoxicity induced by manganese. In conclusion, our studies show that manganese may induce the overexpression of α-synuclein via ERK1/2 activation, which may play a role in manganese-induced cytotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Blotting, Western
  • Cell Separation
  • Enzyme Activation / drug effects
  • Extracellular Signal-Regulated MAP Kinases / drug effects*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Flow Cytometry
  • Manganese / toxicity*
  • PC12 Cells
  • RNA Interference
  • Rats
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Trace Elements / toxicity*
  • alpha-Synuclein / biosynthesis*

Substances

  • Trace Elements
  • alpha-Synuclein
  • Manganese
  • Extracellular Signal-Regulated MAP Kinases