Parkinson Hastalığı ve Akciğer Kanserinde PI3K/Akt Yolağı Faktörlerinin Ekspresyon Düzeylerinin Karşılaştırılması

Abstract

DOI: 10.26650/experimed.2018.18003

Amaç: Parkinson hastalığı (PH) kırk yaş üzeri popülasyonun %0,2’ni etkileyen en sık görülen nörodejeneratif hastalıklardan biridir. Yapılan çalışmalarla PH’de kanser prevalansının düşük olduğu gösterilmiştir. Bu sonuçlar sebebiyle fosfoinositidil-3-kinaz (PI3K)/Akt sağkalım yolağı dikkatleri çekmiştir. Bu yolağa ait gen ekspresyon değişikliklerinin incelenmesi, PH tedavi ve biyobelirteçlerinin bulunması amaçlanmıştır.

Gereç ve Yöntem: Çalışmamızda, PH, akciğer kanseri (AK) hastalarından ve sağlıklı kontrollerden alınan periferik kan mononükleer hücrelerinde DJ-1-PI3K/Akt sinyal yolağı komponentlerinin ve bu yolağı etkileyen proteinlerin ekspresyonu ölçülmüş, ekspresyon düzeylerinin PH’nin klinik parametreleri ile korelasyonu araştırılmıştır.

Bulgular: Fosfataz ve tensin homolog (PTEN) ve mitokondriyal apoptoz-indükleyici faktör 1 (Aifm1)’in PH’de sağlıklı kontrollere göre anlamlı derecede azaldığı ve insülin-benzeri büyüme faktörü (IGF-1)’in anlamlı derecede arttığı saptandı. AK hastalarında ise PTEN, kaspaz-3 ve α-sinükleinin ekspresyonlarının anlamlı derece arttığı, IGF-1’in anlamlı derecede azaldığı saptandı. Ayrıca α-sinüklein, IGF-1, kaspaz-3, DJ-1, memeli hedef rapamisin (mTOR), Mdm2 ve Akt-1 faktörleriyle PH’nin klinik alt tipleri arasında korelasyon belirlendi.

Sonuç: Pro-apoptotik PTEN ve anti-apoptotik PI3K/Akt yolağının ekspresyon seviyelerinde görülen değişiklik PH’de artan nöronal yıkımı kompanse etmek amacıyla anti-apoptotik yolaklarının etkinleştirildiğini düşündürmektedir. Çeşitli PI3K/Akt yolağı ekspresyon düzeyleri ile klinik parametreler arasında korelasyon saptanması PH olgularında bu faktörlerin özürlülük ve prognoz belirteci olarak kullanılabileceğini göstermektedir. Özellikle postural instabilite ile anti-apoptotik faktör arasındaki ekspresyon değişikliği nöronal yıkımı akla getirmektedir.

Keywords

• Parkinson Hastalığı,apoptoz,PTEN,alfa-sinüklein,PI3K/Akt,PI3K/Akt

Comparison of The Expression Levels of PI3K/Akt Pathway Factors in Parkinson’s Disease and Lung Cancer

Abstract

DOI: 10.26650/experimed.2018.18003

Objectives: Parkinson’s disease (PD) is a common neurodegenerative disorder that affects >0.2% of the population aged >40 years. Several studies have reported a low prevalence of cancer in individuals with PD. Therefore, the PI3K/Akt signaling pathway has received increasing research attention. Investigating variations in expression levels of components associated with this pathway might aid in improving novel treatment methods and biomarkers for PD.

Material and Method: We evaluated expression levels of components of the DJ-1-PI3K/Akt signaling pathway in the peripheral blood mononuclear cells of patients with PD, those with lung cancer (LC), and healthy controls and attempted to identify a possible correlation between expression levels and clinical features of PD.

Results: Levels of phosphatase and tensin homolog (PTEN) and apoptosis-inducing factor-1 significantly decreased, whereas those of insulin-like growth factor 1 (IGF-1) significantly increased in patients with PD than in healthy controls. In patients with LC, levels of PTEN, caspase-3, and α-synuclein significantly increased, whereas those of IGF-1 significantly decreased. Furthermore, a correlation was observed between the clinical subtypes of PD and levels of α-synuclein, IGF-1, caspase-3, DJ-1, mechanistic target of rapamycin, Mdm2, and Akt-1 factors.

Conclusion: Patients with PD showed decreased expression levels of proapoptotic PTEN and increased levels of components of the antiapoptotic PI3K/Akt pathway, which suggests an activation of the antiapoptotic pathway to compensate for the increased neuronal destruction in PD. The correlation between expression levels of components of several PI3K/Akt signaling pathway and clinical parameters suggests that these factors can be used as disability and prognostic markers in patients with PD. Decreased expression levels of antiapoptotic factors in patients with PD having postural instability, in particular, suggests a close relationship between neuronal destruction and this symptom.

Keywords

• Parkinson’s Disease,apoptosis,PTEN,alpha-synuclein,PI3K/Akt

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