The anti-apoptotic mechanism of metformin against apoptosis induced by ionizing radiation in cultured human blood lymphocytes

Sedighe Kolivand, Elahe Motevaseli, Mohsen Cheki, Aziz Mahmoudzadeh, Alireza Shirazi, Vuk Fait


Background: In a previous article, we have shown that metformin (MET) can reduce IR-induced apoptosis in cultured human blood lymphocytes. However, the anti-apoptotic mechanism of MET against IR remains unclear. The present study attempts to investigate the mechanism of action of MET in limiting X-ray-induced apoptosis in cultured human blood lymphocytes.

Materials and Methods: Human lymphocytes were treated with MET for 2 h and irradiated with 6 MV X-rays. The gene expression levels of BAX, CASP3 and BCL2 were determined 24 h post-irradiation using real-time quantitative PCR technique. Furthermore, the protein levels of BAX, CASP3 and BCL2 were analyzed by western blotting assay.

Results: Radiation exposure increased the expressions of BAX and CASP3 genes, and decreased the expression of BCL2 gene in lymphocytes. Conversely, an increase in BCL2 gene expression along with a decrease in BAX and CASP3 genes expression was observed in MET plus irradiated lymphocytes. It was found that radiation increased BAX/BCL2 ratio, while MET pretreatment reduced these ratio. Also, treatment with MET without irradiation did not change in the expressions of BAX, CASP3 and BCL2 genes. On the other hand, down-regulated the expression of BCL2 protein and up-regulated the expressions of BAX and CASP3 proteins were found in 2 Gy-irradiated lymphocytes, while pretreatment with MET significantly reversed this tendency.

Conclusion: The result suggest that MET can protect of lymphocytes against apoptosis induced by IR through induction of cellular anti-apoptotic signaling.

Klíčová slova

ionizing radiation;metformin;anti-apoptotic;lymphocytes;mechanism

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