Aim and scope: 

The haematopoietic factor erythropoietin (EPO) has recently been recognized to play a physiological role in cellular survival. In vitro studies have shown that EPO has direct effects on proliferation and cell death in proximal tubular epithelial cells. Recently, it has been reported that mitochondrial K-ATP channel openers have an effect on myocardial protection via a pharmacological preconditioning action with EPO. The studies related to role of K-ATP channels in renal ischemia pathophysiology and they have conflicting results. In this study we aimed to evaluate effect of K-ATP channels blocker glybenclamide and opener diazoxide in hypoxia and EPO treatment.

Methods and material: 

In this study; human renal proximal tubular cell line CRL-2830 incubated with EPO (20 iu/ml), glybenclamide (100 mM) and diazoxide (100 mM) at the 2-24-48^th hours. Apoptotic activity, (caspase-3 levels), cellular proliferation (MTT) and expression of Kir6X channels was evaluated with western blot.

Results: 

EPO induced prominent proliferation in renal tubuler cells. Erythropoietin attenuates hypoxia-induced apoptosis of tubular cells in a dose-time dependent manner. Diazoxide has similar effect with EPO. Glybenclamide decrased cellular proliferation, induced caspase-3 activity, apoptosis and cell death. Glybenclamide blocked protective role of EPO. EPO treatment increased Kir 6.1 and 6.2 expression while glybenclamide decreased.

Conclusions: 

EPO and diazoxide treatment are found protective against hypoxia induced cytotoxicity. K-ATP channels are important for regulation of metabolic and acid-base balance of the cells, especially for renal tubular functions. Glybenclamide is currently used as an antidiabetic and renal pathologies are very common in progress of diabetes. Our results might be informative for regulation of treatment protocols of diabetic patients.

This study is supported by TUBITAK (SBAG-108S248).