DOI: 10.37212/jcnos.1434545 ISSN: 2149-7222

Neuroprotective action of honey bee venom (melittin) against hypoxiainduced oxidative toxicity and cell death via inhibition of the TRPM2 channel

Kemal ERTİLAV
  • Cell Biology
  • Cellular and Molecular Neuroscience
  • Molecular Biology
  • Biochemistry
  • Biophysics
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One bioactive element of honeybee venom is melittin (MEL). MEL induced oxidant and apoptotic activities through the increase of mitochondrial Zn2+ and Ca2+ in tumor cells, but it also induced neuroprotective activity by inhibiting the cell death, intracellular reactive oxygen species (iROS), and mitochondrial ROS (mROS) productions in neurons. By stimulating the TRPM2 channel, hypoxia (HPO) enhances the effects of oxidative stress and neuronal death; however, its inhibition prevents the alterations. I studied the neuroprotective effect of MEL on HPO-mediated oxidative neurotoxicity and cell death in SH-SY5Y neuronal cells by altering the TRPM2 signaling pathways. In the SH-SY5Y cells, five groups were induced as control, MEL (1 ug/ml for 24 hrs), HPO (CoCl2 and 200 M for 24 hrs), HPO + MEL, and HPO + TRPM2 antagonist (2-aminoethoxydiphenyl borate, 2APB) (100 M for 2 hrs). The amounts of cytosolic free Ca2+ were increased in the HPO group by the stimulation of hydrogen peroxide, although they were decreased in the cells by the treatment of 2APB and MEL. The amount of cytosolic free Ca2+ was higher in the HPO group than in the control group. The amounts of cell death (propidium iodide positive cell number), oxidants (mROS and iROS), mitochondrial membrane depolarization, and cytosolic free Zn2+ were higher in the HPO group than in the control and MEL groups, although their amounts were lower in the HPO + MEL and HPO + 2APB groups than in the HPO group only. In conclusion, MEL therapy reduced the amount of HPO-induced oxidative stress and neuronal deaths in SH-SY5Y cells by inhibiting TRPM2. The MEL could be considered as a potential protective component against oxidative neuronal damage caused by HPO.

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