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PC12 hücrelerinde 1-metil 4-fenilpridinyum (MPP+) ile olusturulan deneysel parkinson modelinde Zonisamid'in CA+2 sinyali, oksidatif stres, hücre canlılığı, kaspaz aktivitesi üzerine etkisi = The effect of zonisamide induced by the 1-methyl 4-phenylpyrdinium (MPP+) model of experimental parkinson's on the CA+2 signaling, oxidative stress, cell viability, caspase activity in PC12 cells /

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dc.creator Gürler, Semih. author 23908
dc.creator Yürekli, Vedat Ali, 1974- thesis advisor 18515
dc.creator Nazıroğlu, Mustafa, 1968- thesis advisor 10271
dc.creator Süleyman Demirel Üniversitesi. Tıp Fakültesi. Nöroloji Anabilim Dalı. issuing body 11613
dc.date 2011.
dc.date.accessioned 2025-02-25T10:49:06Z
dc.date.available 2025-02-25T10:49:06Z
dc.identifier http://tez.sdu.edu.tr/Tezler/TT00648.pdf
dc.identifier.uri http://acikerisim.sdu.edu.tr/xmlui/handle/123456789/102685
dc.description Parkinson hastalığı, dopamin üreten hücrelerin dejenerasyonunun neden olduğu kesin tedavisi olmayan, motor ve non-motor semptomlarla karekterize, sinsi baslangıçlı progresif nörodejeneratif bir hastalıktır. Dünyada, esasen bir antiepileptik olarak kullanılan Zonisamid (1,2- benzisoxazole-3-methaesulfonamide) molekülü benzisoxole yapısında uzun yarı ömürlü (63 saat) iyi tolere edilen bir ilaçtır. Yapılan klinik ve deneysel arastırmalarda, Parkinson hastalarının motor fonksiyonlarında iyilesme sağladığı gösterilmistir ve nöroprotektif ve oksidatif stres üzerinde etkili olduğu saptanmıstır. Biz çalısmamızda, PC12 nöronal hücreleri üzerinde MPP+ ile oluşturulan deneysel Parkinson modelinde, Zonisamidin oksidatif stres, hücre canlılığı, Ca+2 sinyali, kaspaz aktivitesi üzerine etkisini arastırmayı amaçladık. PC12 hücreleri, 1. Grup (Kontrol grubu), 2. Grup (ZNS grubu), 3. Grup (MPP+), 4. Grup (ZNS+MPP+ grubu) olmak üzere 4 gruba ayrıldı. ZNS ve MPP+.nin doz ve süreleri hücre canlılığını değerlendirmede kullanılan MTT analizine göre belirlendi. Hücreler, 100 .M ZNS ile 5 saat, 100 .M MPP+ ile 10 saat ve MPP+ ve ZNS ile 10 saat boyunca inkübe edildi.Lipid peroksidasyon düzeyleri, MPP+ grubunda (p<0.05) anlamlı olarak yüksek bulunurken,ZNS (p<0.05) ve ZNS+MPP+ (p<0.05) grubunda, anlamlı olarak düsük saptandı. GSH düzeyleri, MPP+ grubunda (p<0.05) anlamlı olarakdüşük saptanırken, ZNS (p<0.01) ve ZNS+MPP+(p<0.01) grubunda anlamlı olarak yüksek tespit edildi. GSH-Px düzeyleri MPP+(p<0.05) grubunda, anlamlı olarak düsük tespit edilirken, ZNS (p<0.001) ve ZNS+MPP+ (p<0.01) gruplarında anlamlı olarak yüksek tespit edildi. Sitozole Ca+2 salınımı, MPP+ (P<0.001) ve ZNS+MPP+(p<0.01) grubunda, anlamlı düzeyde artmıs olarak bulunurken, ZNS (p<0.01) grubunda, anlamlı olarak düsük düzeyde saptandı. MPP+ grubuna kıyasla ZNS+MPP+(p<0.01) grubunda sitozole Ca+2 salınımı anlamlı olarak düsük tespit edildi. Kaspaz-3 aktivitesi, MPP+ grubuna kıyasla ZNS grubunda anlamlıolarak düsük tespit edildi(p<0.001). Sonuç olarak, bu çalısmada ZNS'in, deneysel Parkinson modelinde oksidatif stres, hücre içi Ca+2 hemostazı, hücre canlılığı ve apopitoz üzerine koruyucu etkisi gözlenmistir. Anahtar Kelimeler : Parkinson Hastalığı, Zonisamid, MPP+, PC12 hücresi, Oksidatif Stres, Ca+2 Salınımı, Kaspaz-3, Apopitozis.
dc.description Parkinson's is a incurable progressive neurological condition caused by a degeneration of dopamine-producing cells charecterized by motor and non-motor symptoms. In fact, zonisamide is used as an antiepileptic molecule in the world and benzisoxole (1,2 benzisoxazole-3-methaesulfonamide) is a moleculer structure of zonisamide which has a long half-life (63 hours) and a well tolerateddrug. ZNS revealed evidence of an effect onimproves motor function in with Parkinson's patient that on oxidative stress and neuroprotective in clinical and experimental research. In clinical and experimental research, improvement in motor functions of Parkinson's patients was revealed and its effect on neuroprotective and oxidative stress has been identified. In our study, we aimed to investigate to the effect of zonisamide on the oxidative stress, cell viability, Ca+2 signal, kaspas activity that induced by the MPP+ model of Parkinson's in neuronal PC12 cells. PC12 cells were divided into 4 groups namely, Group 1 (control group), Group 2 (ZNS group), Group 3 (MPP +), Group 4 (ZNS + MPP + group). The dose and duration of ZNS and MPP+, were determined according to MTT analysis which used to assessed the cell viability. The cells were incubated to for 5 hours with 100 .m ZNS, 10 hours with 100 .M MPP+ and 10 hours with ZNS and MPP+. Lipid peroxidation levels were found significantly higher in the MPP+ group, (p <0.05) these levels were significantly lower in ZNS (p <0.05) and the ZNS+MPP+ (p <0.05) group. While GSH levels were found significantly lower in the MPP+ group, (p <0.05) it was found significantly higher in the ZNS (p <0.01) and the ZNS+MPP+ (p <0.01) group. While GSH-Px levels were found to be significantly lower in the MPP+ (p <0.05) group, it was found to be significantly higher in theZNS (p <0.001) and the ZNS+MPP+ (p <0.01) groups. Cytosolic Ca+2 release was found to be significantly increased in the MPP+ (P <0.001) and the ZNS+MPP+ (p <0.01) groups than the ZNS (p <0.01) group. And also according to the MPP+ group ctosolic Ca+2 releasewas found to be significantly decreased in ZNS+MPP+ (p <0.01) group. Caspase-3 activity was found to be significantly lower in the ZNS (p <0.001) group than the MPP+ (p <0.001) group. In conclusion, in this study, in an experimental model of Parkinson disease ; ZNS has been observed to protectiveeffect on the oxidative stress, intracellular Ca+2 hemostasis, cell viability and the apoptosis. Keywords : Parkinson's Disease, Zonisamide, MPP+, PC12 Cells, Oxidative Stress, Ca+2 Release, Caspase-3, Apoptosis.
dc.description Tez (Uzmanlık)- Süleyman Demirel Üniversitesi, Tıp Fakültesi, Nöroloji Anabilim Dalı, 2011.
dc.description Kaynakça var.
dc.description Parkinson hastalığı, dopamin üreten hücrelerin dejenerasyonunun neden olduğu kesin tedavisi olmayan, motor ve non-motor semptomlarla karekterize, sinsi baslangıçlı progresif nörodejeneratif bir hastalıktır. Dünyada, esasen bir antiepileptik olarak kullanılan Zonisamid (1,2- benzisoxazole-3-methaesulfonamide) molekülü benzisoxole yapısında uzun yarı ömürlü (63 saat) iyi tolere edilen bir ilaçtır. Yapılan klinik ve deneysel arastırmalarda, Parkinson hastalarının motor fonksiyonlarında iyilesme sağladığı gösterilmistir ve nöroprotektif ve oksidatif stres üzerinde etkili olduğu saptanmıstır. Biz çalısmamızda, PC12 nöronal hücreleri üzerinde MPP+ ile oluşturulan deneysel Parkinson modelinde, Zonisamidin oksidatif stres, hücre canlılığı, Ca+2 sinyali, kaspaz aktivitesi üzerine etkisini arastırmayı amaçladık. PC12 hücreleri, 1. Grup (Kontrol grubu), 2. Grup (ZNS grubu), 3. Grup (MPP+), 4. Grup (ZNS+MPP+ grubu) olmak üzere 4 gruba ayrıldı. ZNS ve MPP+.nin doz ve süreleri hücre canlılığını değerlendirmede kullanılan MTT analizine göre belirlendi. Hücreler, 100 .M ZNS ile 5 saat, 100 .M MPP+ ile 10 saat ve MPP+ ve ZNS ile 10 saat boyunca inkübe edildi.Lipid peroksidasyon düzeyleri, MPP+ grubunda (p<0.05) anlamlı olarak yüksek bulunurken,ZNS (p<0.05) ve ZNS+MPP+ (p<0.05) grubunda, anlamlı olarak düsük saptandı. GSH düzeyleri, MPP+ grubunda (p<0.05) anlamlı olarakdüşük saptanırken, ZNS (p<0.01) ve ZNS+MPP+(p<0.01) grubunda anlamlı olarak yüksek tespit edildi. GSH-Px düzeyleri MPP+(p<0.05) grubunda, anlamlı olarak düsük tespit edilirken, ZNS (p<0.001) ve ZNS+MPP+ (p<0.01) gruplarında anlamlı olarak yüksek tespit edildi. Sitozole Ca+2 salınımı, MPP+ (P<0.001) ve ZNS+MPP+(p<0.01) grubunda, anlamlı düzeyde artmıs olarak bulunurken, ZNS (p<0.01) grubunda, anlamlı olarak düsük düzeyde saptandı. MPP+ grubuna kıyasla ZNS+MPP+(p<0.01) grubunda sitozole Ca+2 salınımı anlamlı olarak düsük tespit edildi. Kaspaz-3 aktivitesi, MPP+ grubuna kıyasla ZNS grubunda anlamlıolarak düsük tespit edildi(p<0.001). Sonuç olarak, bu çalısmada ZNS'in, deneysel Parkinson modelinde oksidatif stres, hücre içi Ca+2 hemostazı, hücre canlılığı ve apopitoz üzerine koruyucu etkisi gözlenmistir. Anahtar Kelimeler : Parkinson Hastalığı, Zonisamid, MPP+, PC12 hücresi, Oksidatif Stres, Ca+2 Salınımı, Kaspaz-3, Apopitozis.
dc.description Parkinson's is a incurable progressive neurological condition caused by a degeneration of dopamine-producing cells charecterized by motor and non-motor symptoms. In fact, zonisamide is used as an antiepileptic molecule in the world and benzisoxole (1,2 benzisoxazole-3-methaesulfonamide) is a moleculer structure of zonisamide which has a long half-life (63 hours) and a well tolerateddrug. ZNS revealed evidence of an effect onimproves motor function in with Parkinson's patient that on oxidative stress and neuroprotective in clinical and experimental research. In clinical and experimental research, improvement in motor functions of Parkinson's patients was revealed and its effect on neuroprotective and oxidative stress has been identified. In our study, we aimed to investigate to the effect of zonisamide on the oxidative stress, cell viability, Ca+2 signal, kaspas activity that induced by the MPP+ model of Parkinson's in neuronal PC12 cells. PC12 cells were divided into 4 groups namely, Group 1 (control group), Group 2 (ZNS group), Group 3 (MPP +), Group 4 (ZNS + MPP + group). The dose and duration of ZNS and MPP+, were determined according to MTT analysis which used to assessed the cell viability. The cells were incubated to for 5 hours with 100 .m ZNS, 10 hours with 100 .M MPP+ and 10 hours with ZNS and MPP+. Lipid peroxidation levels were found significantly higher in the MPP+ group, (p <0.05) these levels were significantly lower in ZNS (p <0.05) and the ZNS+MPP+ (p <0.05) group. While GSH levels were found significantly lower in the MPP+ group, (p <0.05) it was found significantly higher in the ZNS (p <0.01) and the ZNS+MPP+ (p <0.01) group. While GSH-Px levels were found to be significantly lower in the MPP+ (p <0.05) group, it was found to be significantly higher in theZNS (p <0.001) and the ZNS+MPP+ (p <0.01) groups. Cytosolic Ca+2 release was found to be significantly increased in the MPP+ (P <0.001) and the ZNS+MPP+ (p <0.01) groups than the ZNS (p <0.01) group. And also according to the MPP+ group ctosolic Ca+2 releasewas found to be significantly decreased in ZNS+MPP+ (p <0.01) group. Caspase-3 activity was found to be significantly lower in the ZNS (p <0.001) group than the MPP+ (p <0.001) group. In conclusion, in this study, in an experimental model of Parkinson disease ; ZNS has been observed to protectiveeffect on the oxidative stress, intracellular Ca+2 hemostasis, cell viability and the apoptosis. Keywords : Parkinson's Disease, Zonisamide, MPP+, PC12 Cells, Oxidative Stress, Ca+2 Release, Caspase-3, Apoptosis.
dc.language tur
dc.publisher Isparta : SDÜ Tıp Fakültesi,
dc.subject Süleyman Demirel Üniversitesi
dc.title PC12 hücrelerinde 1-metil 4-fenilpridinyum (MPP+) ile olusturulan deneysel parkinson modelinde Zonisamid'in CA+2 sinyali, oksidatif stres, hücre canlılığı, kaspaz aktivitesi üzerine etkisi = The effect of zonisamide induced by the 1-methyl 4-phenylpyrdinium (MPP+) model of experimental parkinson's on the CA+2 signaling, oxidative stress, cell viability, caspase activity in PC12 cells /
dc.type text


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