Protective effect of (+/-) isoborneol against 6-OHDA-induced apoptosis in SH-SY5Y cells

Cell Physiol Biochem. 2007;20(6):1019-32. doi: 10.1159/000110682. Epub 2007 Oct 29.

Abstract

Oxidative stress caused by dopamine (DA) may play an important role in the pathogenesis of Parkinson's disease (PD). (+/-) Isoborneol is a monoterpenoid alcohol present in the essential oils of numerous medicinal plants and is a known antioxidant. In this study, we investigated the neuroprotective effect of isoborneol against 6-hydroxydopamine (6-OHDA)-induced cell death in human neuroblastoma SH-SY5Y cells. Pretreatment of SH-SY5Y cells with isoborneol significantly reduced 6-OHDA-induced generation of reactive oxygen species (ROS) and 6-OHDA-induced increases in intracellular calcium. Furthermore, apoptosis induced by 6-OHDA was reversed by isoborneol treatment. Isoborneol protected against 6-OHDA-induced increases in caspase-3 activity and cytochrome C translocation into the cytosol from mitochondria. Isoborneol prevented 6-OHDA from decreasing the Bax/Bcl-2 ratio. We also observed that isoborneol decreased the activation of c-Jun N-terminal kinase and induced activation of protein kinase C (PKC) which had been suppressed by 6-OHDA. Our results indicate that the protective function of isoborneol is dependent upon its antioxidant potential and strongly suggest that isoborneol may be an effective treatment for neurodegenerative diseases associated with oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Calcium / metabolism
  • Camphanes / pharmacology*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Survival / drug effects
  • Cytochromes c / metabolism
  • Cytoprotection / drug effects*
  • Dose-Response Relationship, Drug
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Oxidation-Reduction / drug effects
  • Oxidopamine / pharmacology*
  • Phosphoproteins / metabolism
  • Phosphorylation / drug effects
  • Protein Kinase C / metabolism
  • Reactive Oxygen Species / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Camphanes
  • Phosphoproteins
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • Oxidopamine
  • Cytochromes c
  • Protein Kinase C
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Caspase 3
  • isoborneol
  • Calcium