Synphilin-1 has neuroprotective effects on MPP +-induced Parkinson's disease model cells by inhibiting ROS production and apoptosis

Neurosci Lett. 2019 Jan 18;690:145-150. doi: 10.1016/j.neulet.2018.10.020. Epub 2018 Oct 11.

Abstract

Synphilin-1, a cytoplasmic protein, interacts with α-synuclein which is one of the main constituents of Lewy bodies and plays an important role in the pathology of Parkinson's disease (PD), in neurons. This interaction indicates that synphilin-1 may also play a central role in PD. However, the biological functions of synphilin-1 are not fully understood, and whether synphilin-1 is neurotoxic or neuroprotective remains controversial. This study examined the function of synphilin-1 in a PD model in vitro. We used an inhibitor of mitochondrial complex I, 1-methyl-4-phenylpyridinium (MPP+). We established human neuroblastoma SH-SY5Y cell lines that stably expressed human synphilin-1. We found that overexpression of synphilin-1 increased SH-SY5Y cell viability after MPP+ treatment. We further found that synphilin-1 significantly suppressed apoptotic changes in nuclei, including nuclear condensation and fragmentation, after MPP+ treatment. We showed that synphilin-1 significantly decreased MPP+-induced cleaved caspase-3 and cleaved poly-ADP-ribose polymerase levels by using western blotting. Production of reactive oxygen species (ROS) induced by MPP+ was significantly reduced in cells expressing synphilin-1 compared to those expressing empty vector. Synphilin-1 inhibited MPP+-induced cytochrome c release from mitochondria into the cytosol. These data suggested that synphilin-1 may function to protect against dopaminergic cell death by preserving mitochondrial function and inhibiting early steps in the intrinsic apoptotic pathway. Taken together, our results indicated that synphilin-1 may play neuroprotective roles in PD pathogenesis by inhibiting ROS production and apoptosis.

Keywords: Apoptosis; Dopaminergic neurodegeneration; MPP(+); Parkinson’s disease; synphilin-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenylpyridinium / toxicity*
  • Apoptosis / drug effects*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Caspase 3 / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cytochromes c / metabolism
  • Gene Knockdown Techniques
  • Humans
  • MPTP Poisoning / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neuroprotective Agents / metabolism*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Reactive Oxygen Species / metabolism*
  • Transfection
  • Up-Regulation

Substances

  • Carrier Proteins
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • SNCAIP protein, human
  • Cytochromes c
  • Poly(ADP-ribose) Polymerases
  • Caspase 3
  • 1-Methyl-4-phenylpyridinium