KARDİYAK ENERJİ METABOLİZMASINDA β-ARRESTİN PROTEİNLERİNİN ROLÜ

Öz

Amaç: β-arrestinler G-proteini ile kenetli reseptörlerin (GPKR) sinyallerini düzenleyen proteinlerdir. Bu proteinler, agonist ve bias agonist ligandların metabolic ve fonksiyonel etkilerine aracılık ederler. Bu çalışmada, β-arrestinlerin kardiyak substrat metabolizması üzerindeki potansiyel etkilerinin değerlendirilmesi amaçlanmıştır.

Gereç ve Yöntem: G-proteinlerinin etkisini ortadan kaldırmak ve sadece β-arrestin sinyaline odaklanabilmek için bir β-arrestin-bias agonist olan karvedilol kullanılmıştır. Kontrol fare kalplerinde karvedilol uygulaması sonrası glukoz ve palmitat oksidasyonundaki değişiklikler değerlendirilmiştir. Protein kinaz B (Akt), ekstrasellüler sinyal düzenleyici kinaz (ERK) ve pirüvat dehidrogenaz (PDH) fosforilasyonları Western blot yöntemi ile değerlendirilmiştir. Ayrıca H9c2 hücre hattında fenilefrin ile hipertrofi oluşturulmuş; karvedilol veya prazosin-tedavili hücrelerde glukoz metabolizması değerlendirilmiştir.

Sonuç ve Tartışma: Karvedilol kontrol fare kalplerinde glukoz ve palmitat oksidasyonunu etkilememiştir. Öte yandan akut karvedilol uygulaması bu kalplerde ERK ve PDH fosforilasyonlarını değiştirmiştir. Hipertrofik H9c2 hücrelerde karvedilol tedavisi glikolizi azaltmış ve glukoz oksidasyonunu artırmıştır. Bu durum hipertrofide bozulmuş olan glikoliz-glukoz oksidasyonu kenetlenmesinde düzelmeye aracılık etmiştir. Sonuç olarak karvedilol ve β-arrestin proteinlerinin glukoz metabolizmasını iyileştirebileceği sonucuna ulaşılmıştır.

Anahtar Kelimeler

• β-arrestin
• glikoliz
• glukoz oksidasyonu
• karvedilol
• palmitat oksidasyonu

THE ROLE OF β-ARRESTIN PROTEINS IN CARDIAC ENERGY METABOLISM

Öz

Objective: β-arrestins are G-protein coupled receptor (GPCR) signal regulation proteins. These proteins are involved in metabolic or functional effects of agonist and biased agonist ligands. The aim of this study was to evaluate the potential effects of β-arrestins on cardiac substrate metabolism.

Material and Method: To eliminate G-protein effects and to focus specifically on the β-arrestin signal, we used carvedilol, a β-arrestin-biased agonist. Changes in glucose and palmitate oxidation after carvedilol administration were assessed in control mouse hearts. Western blotting was used to evaluate the phosphorylation levels of protein kinase B (Akt), extracellular signal-regulated kinase (ERK) and pyruvate dehydrogenase (PDH) proteins in these hearts.  Hypertrophy was induced with phenylephrine in H9c2 cells. Glucose metabolism was measured in cells treated with carvedilol or prazosin using insulinated perfusate.

Result and Discussion: Carvedilol did not alter glucose or palmitate oxidation rates in control mouse hearts. However acute administration of carvedilol influenced ERK and PDH phosphorylation in the hearts. In hypertrophied H9c2 cells, carvedilol treatment decreased glycolysis and slightly increased glucose oxidation which resulted in a significant amelioration in glycolysis-glucose oxidation coupling. In conclusion, carvedilol and β-arrestins may improve glucose metabolism.

Anahtar Kelimeler

• β-arrestin
• carvedilol
• glycolysis
• glucose oxidation
• palmitate oxidation

Kaynakça

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