Sulfated Polysaccharide Isolated from the Sea Cucumber Stichopus japonicus Against PC12 Hypoxia/Reoxygenation Injury by Inhibition of the MAPK Signaling Pathway

Cell Mol Neurobiol. 2015 Nov;35(8):1081-92. doi: 10.1007/s10571-015-0202-x. Epub 2015 May 8.

Abstract

In this report, the sulfated polysaccharide (SJP) isolated from the sea cucumber Stichopus japonicus can protect PC12 from Na2S2O4-induced hypoxia/reoxygenation (H/R) injury. SJP effectively improves cell viability and reduces extracellular LDH release in PC12 cells after H/R. Moreover, SJP significantly increases SOD activity but decreases MDA levels. Our experiments showed that SJP could significantly reduce cell apoptosis caused by H/R. Our current results demonstrate that SJP suppressed the activation of MAPKs, resulting in a significant decrease in Bax/Bcl-2 ratio, cleaved caspase-3/caspase-3, p53 phosphorylation, and cytochrome c release in a concentration-dependent manner. MAPK is closely related to H/R injury. SJP inhibited JNK1/2 and p38 MAPK activation but did not affect the increased ERK1/2 expression. These results suggested that JNK1/2 and p38 MAPK pathways could be involved in SJP-mediated attenuation of PC12 H/R injury. SJP prevented PC12 H/R injury in a dose-dependent manner, indicating that SJP may be developed as a candidate drug to prevent or treat cerebral ischemia-reperfusion injury.

Keywords: Hypoxia/reoxygenation(H/R); MAPK; Na2S2O4; PC12.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Hypoxia / drug effects
  • Cell Hypoxia / physiology
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dose-Response Relationship, Drug
  • MAP Kinase Signaling System / drug effects*
  • MAP Kinase Signaling System / physiology
  • PC12 Cells
  • Polysaccharides / isolation & purification*
  • Polysaccharides / pharmacology*
  • Protein Kinase Inhibitors / isolation & purification*
  • Protein Kinase Inhibitors / pharmacology*
  • Rats
  • Sea Cucumbers
  • Stichopus*

Substances

  • Polysaccharides
  • Protein Kinase Inhibitors