Zonisamide Attenuates MPP(+)-Induced Oxidative Toxicity Through Modulation of Ca2+ Signaling and Caspase-3 Activity in Neuronal PC12 Cells


YÜREKLİ V. A. , Gurler S., NAZIROĞLU M. , Uguz A. C. , KOYUNCUOĞLU H. R.

CELLULAR AND MOLECULAR NEUROBIOLOGY, cilt.33, ss.205-212, 2013 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 33 Konu: 2
  • Basım Tarihi: 2013
  • Doi Numarası: 10.1007/s10571-012-9886-3
  • Dergi Adı: CELLULAR AND MOLECULAR NEUROBIOLOGY
  • Sayfa Sayıları: ss.205-212

Özet

Parkinson's disease is an incurable progressive neurological condition caused by a degeneration of dopamine-producing cells characterized by motor and non-motor symptoms. The major mechanisms of the antiepileptic actions of ZNS are inhibition of voltage-gated Na+ channel, T-type voltage-sensitive Ca2+ channel, Ca2+-induced Ca2+ releasing system, and neuronal depolarization-induced glutamate release; and enhancement of release of inhibitory neurotransmitters; however, the detailed mechanism of antiparkinsonian effects of ZNS remains to be clarified. We aimed to investigate to the effect of ZNS on the oxidative stress, cell viability, Ca2+ signaling, and caspase activity that induced by the MPP+ model of Parkinson's in neuronal PC12 cells. Neuronal PC12 cells were divided into four groups namely, control, ZNS, MPP+, and ZNS+MPP+ groups. The dose and duration of ZNS and MPP+ were determined according to cell viability (MTT) analysis which used to assess the cell viability. The cells in ZNS, MPP+, and ZNS+MPP+ groups were incubated for 5 h with 100 mu M ZNS, 10 h with 100 mu M MPP+, and 10 h with ZNS and MPP+, respectively. Lipid peroxidation and cytosolic free Ca2+ concentrations were higher in the MPP+ group than in control although their levels were lower in ZNS and the ZNS+MPP+ groups than in control. Reduced glutathione and glutathione peroxidase values were lower in the MPP+ group although they were higher in the ZNS and the ZNS+MPP+ groups than in control. Caspase-3 activity was lower in the ZNS group than in the MPP+ group. In conclusion, ZNS induced modulator effects on the oxidative stress, intracellular Ca2+, and the caspase-3 values in an experimental model of Parkinson disease.