Protective Effect of Fucoidan against MPP+-Induced SH-SY5Y Cells Apoptosis by Affecting the PI3K/Akt Pathway

Mar Drugs. 2020 Jun 25;18(6):333. doi: 10.3390/md18060333.

Abstract

The main pathologic changes of the Parkinson's disease (PD) is dopaminergic (DA) neurons lost. Apoptosis was one of the important reasons involved in the DA lost. Our previous study found a fucoidan fraction sulfated heterosaccharide (UF) had neuroprotective activity. The aim of this study was to clarify the mechanism of UF on DA neurons using human dopaminergic neuroblastoma (SH-SY5Y) cells a typical as a PD cellular model. Results showed that UF prevented MPP+-induced SH-SY5Y cells apoptosis and cell death. Additionally, UF pretreated cells increased phosphorylation of Akt, PI3K and NGF, which means UF-treated active PI3K-Akt pathway. Moreover, UF treated cells decreased the expression of apoptosis-associated protein, such as the ratio of Bax/Bcl-2, GSK3β, caspase-3 and p53 nuclear induced by MPP+. This effect was partially blocked by PI3K inhibitor LY294002. Our data suggested that protective effect of UF against MPP+-induced SH-SY5Y cells death by affecting the PI3K-Akt pathway. These findings contribute to a better understanding of the critical roles of UF in treating PD and may elucidate the molecular mechanisms of UF effects in PD.

Keywords: PI3K–Akt; dopamine neurons apoptosis; fucoidan; sulfated heterosaccharide.

MeSH terms

  • 1-Methyl-4-phenylpyridinium / antagonists & inhibitors
  • 1-Methyl-4-phenylpyridinium / toxicity*
  • Apoptosis / drug effects*
  • Caspases / metabolism
  • Cell Line, Tumor
  • Chromones / pharmacology
  • Humans
  • Morpholines / pharmacology
  • Neuroblastoma
  • Neuroprotective Agents / pharmacology*
  • Parkinson Disease / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Polysaccharides / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction
  • bcl-2-Associated X Protein / metabolism

Substances

  • BAX protein, human
  • BCL2 protein, human
  • Chromones
  • Morpholines
  • Neuroprotective Agents
  • Polysaccharides
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • fucoidan
  • Proto-Oncogene Proteins c-akt
  • Caspases
  • 1-Methyl-4-phenylpyridinium