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

• Published in: Cellular and molecular neurobiology Vol. 33; no. 2; pp. 205 - 212
• Main Authors: Yürekli, Vedat Ali, Gürler, Semih, Nazıroğlu, Mustafa, Uğuz, Abdülhadi Cihangir, Koyuncuoğlu, Hasan Rifat
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-03-2013
• Subjects: 1-Methyl-4-phenylpyridinium - toxicity; Animals; Biomedical and Life Sciences; Biomedicine; Calcium - metabolism; Calcium Signaling - drug effects; Caspase 3 - metabolism; Cell Biology; Cell Survival - drug effects; Cytosol - drug effects; Cytosol - metabolism; Dose-Response Relationship, Drug; Glutathione - metabolism; Glutathione Peroxidase - metabolism; Ions; Isoxazoles - pharmacology; Lipid Peroxidation - drug effects; Neurobiology; Neurons - drug effects; Neurons - enzymology; Neurons - pathology; Neurosciences; Original Research; Oxidative Stress - drug effects; PC12 Cells; Rats; Zonisamide; Neuronal PC12 cells; Oxidative stress; signaling; MPP; Ca; Zonisamide; Apoptosis
• ISSN: 0272-4340; 1573-6830; 1573-6830
• DOI: 10.1007/s10571-012-9886-3

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 Ca
2+
channel, Ca
2+
-induced Ca
2+
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, Ca
2+
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 μM ZNS, 10 h with 100 μM MPP
+
, and 10 h with ZNS and MPP
+
, respectively. Lipid peroxidation and cytosolic free Ca
2+
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 Ca
2+
, and the caspase-3 values in an experimental model of Parkinson disease.