TY  - JOUR
T1  - Rotenon ile İndüklenen İn Vitro Parkinson Hastalığı Modelinde Glukagon Benzeri Peptid-1 Analoğu Ekzenatidin Nöron Sağkalımına Etkisi
TT  - Effect of Glucagon like Peptide-1 Analogue Exenatide on Neuron Survival in Rotenone-Induced In Vitro Parkinson's Disease Model
AU  - Erdoğan, Mümin Alper
AU  - Taşkıran, Dilek
PY  - 2019
DA  - December
DO  - 10.22312/sdusbed.590482
JF  - Süleyman Demirel Üniversitesi Sağlık Bilimleri Dergisi
PB  - Süleyman Demirel Üniversitesi
WT  - DergiPark
SN  - 2146-247X
SP  - 362
EP  - 368
VL  - 10
IS  - 4
LA  - tr
AB  - Parkinson hastalığı (PH), beyinde substansiyanigrada bulunan dopaminerjik nöronların hasarı ve buna eşlik eden striatumdadopamin eksikliği sonucunda gelişen, bradikinezi, rijidite ve posturalinstabilite ile seyreden kronik ve ilerleyici bir nörodejeneratif hastalıktır.Çalışmalar genetik ve yaşlanma, pestisid ve ağır metallere maruziyet gibiçevresel faktörlerin hastalığın etiyopatogenezinde önemli role sahipolabileceğine işaret etmektedir. Rotenon, deneysel PH modeli oluşturmak ve hastalığınmekanizmasını araştırmak amacıyla kullanılan organik bir pestisidtir. Buçalışmada amacımız insan nöroblatoma hücre serisi olan SH-SY5Y hücrelerinderotenonun toksik etkisini ve aynı zamanda GLP-1 analoğu olan ekzenatidinrotenon nörotoksisitesine karşı koruyucu etkili olup olmadığını araştırmaktır.Bu amaçla SH-SY5Y hücre kültürleri çeşitli dozlardaki rotenon ile 24 saatboyunca inkübe edildi. Ekzenatidin koruyucu etkisi yine farklı dozlardakiekzenatidin rotenon ile birlikte kültür medyumuna eklenmesi ve 24 saat inkübeedilmesi ile incelendi. Rotenon ve ekzenatidin etkileri hücre canlılığı,klonojenik aktivite, morfolojik inceleme ve apopitotik hücre ölümünündeğerlendirilmesi ile belirlendi. Sonuçlarımız rotenon eklenen gruplarda dozabağlı olarak ve anlamlı düzeyde hücre canlılığının ve klonojenik aktiviteninazaldığını gösterdi. Ayrıca rotenon eklenen hücrelerde belirgin olarakmorfolojik değişim olduğu ve apopitotik hücre ölümünde artış olduğu gözlendi.Ortama ekzenatidin eklenmesi ise hücre canlılığının ve klonojenik aktiviteninkorunmasına, apopitotik hücre ölümünde azalmaya neden oldu. Sonuç olarak;bulgularımız rotenonun SH-SY5Y hücrelerinde nörotoksik etkilerinin olduğunu ve in vitro PH modeli oluşturmak amacıylakullanılabileceğini gösterdi. Ayrıca, sonuçlarımız ekzenatidin nöronalhücrelerde rotenon ile indüklenen toksisiteye karşı nöroprotektif etkiye sahipolabileceğini gösterdi.
KW  - Parkinson
KW  - Rotenon
KW  - Ekzenatid
KW  - Nörotoksisite
KW  - Nöroprotektif
N2  - Parkinson's disease (PD) is one the most commonneurodegenerative disorder characterized by bradykinesia, tremor, rigidity andpostural instability as a result of progressive degeneration of thedopaminergic neurons in substantia nigra pars compacta (SNc) and dopaminedecrease in the striatum. Accumulating data recommends that combination ofgenetic and environmental factors including aging, exposure to pesticides, andheavy metals may have significant roles in the pathogenesis of PD. Rotenone, anorganic pesticide, is commonly used for investigating the mechanism of neuronaldegeneration in experimental PD models. In the present study, we aimed toinvestigate the effects of rotenone on SH-SY5Y human neuroblastoma cells, andalso the neuroprotective effects of exenatide, a GLP-1 analogue, againstrotenone-induced neurotoxicity. Briefly, to induce rotenone-inducedneurotoxicity, SH-SY5Y cells were exposed to various doses of rotenone for 24hours. To explore the neuroprotective effects of exenatide, different doses ofexenatide were added into the medium with or without rotenone for 24 hours.Cell viability, clonegenic potential, morphological alterations, and apoptoticcell death were evaluated. Our results demonstrated a dose-dependent andsignificant decrease in cell viability in rotenone-exposed groups. Also,rotenone-treated group showed significant morphological alterations, decreasedclonogenic potential and increased apoptosis. However, treatment of the cellswith exenatide significantly improved cell viability and clonogenic activity,and reduced apoptotic cell death. In conclusion, these findings suggested thatrotenone can induce neurotoxicity in neuronal cells and can be used toestablish in vitro PD model. Inaddition, exenatide may have neuroprotective effects on neuronal cells againstrotenone-induced neurotoxicity.
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UR  - https://doi.org/10.22312/sdusbed.590482
L1  - https://dergipark.org.tr/tr/download/article-file/882738
ER  -