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Abstract

Objective: In this study, it was aimed to investigate that PON2, in hypoxia and normoxia in relation to HIF-1α transcription factor that has a role in tumour angiogenesis. Hypoxia inducible factor 1 alpha (HIF-1α) is a transcription factor which is sensitive to hypoxia, causes initiation of angiogenesis and metastasis by providing transcription of numerous genes. As well as hypoxia several inflammatory agents such as lipopolysaccharide (LPS) can regulate the expression of HIF-1α as well as PON2. Oxidative stress is known to have role in cancer. Paraoxonase 2 which is one of the members of paraoxonase family serves as intracellular anti-oxidant. Methods: H1299, A549 ve PC14 non-small cell lung carcinoma cell lines used in this study. Cells were cultured under hypoxia and normoxia conditions with LPS stimulation. HIF-1α and PON2 mRNA expression levels measured by real-time PCR. Western blot studies were performed for protein expression.Results: In this study, it was observed that LPS treatment stimulates HIF-1α expression which increases PON2 expression in NSCLC cell line in under hxpoxia conditions. Conclusion: This study shows that PON2 is regulated by HIF-1α in hypoxia and inflammation. The relationship between hypoxia and inflammation and oxidative status of cells requires further studies

Keywords

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Akciğer kanseri hücre dizilerinde hipoksi indüklenebilir faktör-1 (HIF-1) ve paraoksonaz enzim ilişkisinin araştırılması

Abstract

Giriş: Bu çalışmada tümör anjiyogenezinde önemli rol oynayan hipoksi indüklenebilir faktör 1 (HIF-1) transkripsiyon faktörünün hipoksik ve normoksik koşullarda paraoksonaz 2 (PON2) ile ilişkisinin araştırılması hedeflenmiştir. Hipoksiye duyarlı bir transkripsiyon faktör olan HIF-1α çok sayıda genin transkripsiyonunu sağlayarak anjiyogenez ve metastazın başlamasına yol açar. Hipoksinin yanı sıra lipopolisakkarit (LPS) gibi çeşitli inflamatuvar ajanlar da HIF-1 α’nın ve PON2 nin ekspresyonunu düzenleyebilirler. Oksidatif stres karsinogenezde önemli etiyolojik faktörlerden birisidir. Paraoksonaz ailesi üyelerinden paraoksonaz 2 (PON2) nin hücre içi antioksidan olarak görev yaptığı bilinmektedir.

Yöntemler: H1299, A549 ve PC14 akciğer hücre dizileri normoksi ve hipoksi ortamlarında kültürü yapılarak ve lipopolisakkaritle indüklenerek HIF-1 ve PON2 mRNA ekspresyonları ve western blot tayinleri çalışılmıştır.

Bulgular: Çalışma sonucunda LPS uygulamasının HIF-1α ekspresyonunu uyardığı ve hipoksi koşullarında akciğer hücre dizilerinde PON2 ekspresyonunun arttığı gözlendi.

Sonuç: Bu çalışmada PON 2 enzim ekspresyonunun HIF-1α aracılığıyla hipoksi ve normoksi koşullarında regüle edildiği gözlenmiş olup hipoksi, inflamasyon ve hücrenin oksidatif durumu arasındaki ilişkinin aydınlatılması için ileri çalışmalar gerekebilir.

Anahtar kelimeler: HIF-1α, PON2, LPS, Hipoksi

Keywords

• HIF-1α, PON2, LPS, Hipoksi

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