Bee Venom Protects against Rotenone-Induced Cell Death in NSC34 Motor Neuron Cells

Toxins (Basel). 2015 Sep 21;7(9):3715-26. doi: 10.3390/toxins7093715.

Abstract

Rotenone, an inhibitor of mitochondrial complex I of the mitochondrial respiratory chain, is known to elevate mitochondrial reactive oxygen species and induce apoptosis via activation of the caspase-3 pathway. Bee venom (BV) extracted from honey bees has been widely used in oriental medicine and contains melittin, apamin, adolapin, mast cell-degranulating peptide, and phospholipase A₂. In this study, we tested the effects of BV on neuronal cell death by examining rotenone-induced mitochondrial dysfunction. NSC34 motor neuron cells were pretreated with 2.5 μg/mL BV and stimulated with 10 μM rotenone to induce cell toxicity. We assessed cell death by Western blotting using specific antibodies, such as phospho-ERK1/2, phospho-JNK, and cleaved capase-3 and performed an MTT assay for evaluation of cell death and mitochondria staining. Pretreatment with 2.5 μg/mL BV had a neuroprotective effect against 10 μM rotenone-induced cell death in NSC34 motor neuron cells. Pre-treatment with BV significantly enhanced cell viability and ameliorated mitochondrial impairment in rotenone-treated cellular model. Moreover, BV treatment inhibited the activation of JNK signaling and cleaved caspase-3 related to cell death and increased ERK phosphorylation involved in cell survival in rotenone-treated NSC34 motor neuron cells. Taken together, we suggest that BV treatment can be useful for protection of neurons against oxidative stress or neurotoxin-induced cell death.

Keywords: NSC34 motor neuron cell; bee venom (BV); cleaved caspase-3; phospho-JNK; rotenone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Bee Venoms / pharmacology*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Mice
  • Mitochondria / drug effects
  • Motor Neurons / cytology
  • Motor Neurons / drug effects*
  • Neuroprotective Agents / pharmacology
  • Neurotoxins / toxicity
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism
  • Rotenone / toxicity*

Substances

  • Bee Venoms
  • Neuroprotective Agents
  • Neurotoxins
  • Reactive Oxygen Species
  • Rotenone
  • Casp3 protein, mouse
  • Caspase 3