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

Year 2018, Volume: 8 Issue: 2, 52 - 57, 12.11.2018

Elif Şanlı Nazlı Yalçınkaya Erdem Tüzün

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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