Photoactivation of ERK/CREB/VMAT2 pathway attenuates MPP+-induced neuronal injury in a cellular model of Parkinson's disease

Cell Signal. 2017 Sep:37:103-114. doi: 10.1016/j.cellsig.2017.06.007. Epub 2017 Jun 13.

Abstract

The vesicular monoamine transporter 2 (VMAT2) pumps dopamine from cytoplasm into synaptic vesicles for subsequent release, and the deficits of VMAT2 has been implicated in the dopaminergic neuronal cell loss which is considered as a typical pathological feature of Parkinson's disease (PD). Low-power laser irradiation (LPLI), a potent noninvasive physiotherapy approach, is capable of penetrating into nerve tissue to exert beneficial effects such as promoting nerve regeneration and ATP production. In the present study, we demonstrated that LPLI protects against MPP+-induced neurotoxicity via upregulation of VMAT2 in SH-SY5Y human dopaminergic neuroblastoma cells. The photoactivation of ERK phosphorylated cAMP-response element binding protein (CREB) at Ser133, and thus increased the ability of CREB binding to the promoter region of VMAT2, leading to elevated VMAT2 expression, which contributes to dopamine release and cell survival. Taken together, for the first time to our knowledge, the results showed that LPLI attenuates MPP+-induced neurotoxicity through activation of ERK/CREB/VMAT2 pathway, suggesting that the manipulation of VMAT2 by LPLI may provide a potential therapeutic strategy for PD.

Keywords: Dopamine; LPLI; MPP(+); Parkinson's disease; VMAT2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenylpyridinium*
  • Cell Line, Tumor
  • Cell Survival
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Humans
  • Low-Level Light Therapy*
  • Neurons / cytology
  • Neurons / metabolism
  • Neurons / pathology
  • Neurons / radiation effects
  • Parkinson Disease, Secondary / metabolism
  • Parkinson Disease, Secondary / pathology
  • Parkinson Disease, Secondary / radiotherapy*
  • Signal Transduction / radiation effects*
  • Vesicular Monoamine Transport Proteins / metabolism*

Substances

  • CREB1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • SLC18A2 protein, human
  • Vesicular Monoamine Transport Proteins
  • Extracellular Signal-Regulated MAP Kinases
  • 1-Methyl-4-phenylpyridinium