Role Of Decitabine In The Biogenesis Of Mitochondria Of The Synchronized G0/G1Phase MDS-L Cell Line

Backgroud Myelodysplastic syndrome is a disease origrated from hematological stem cell. Its main characteristic is bone marrow failure, refractory cytopenia in peripheral blood cells and high risk to become AML. DNA hypomethylatic agents have a bright propective for applying in future.DNA methylation transferase1a (DNA Methyltransferase1a, DNMT1a) is an enzyme that maintain the state of DNA methylation, During DNA replication, DNMTla can maintain sub chain of DNA in a state of methylation modification Dectabin as a DNMTI (DNA Methyltransferase Inhibitor),can promote the degradation of DNMTla and reduce the genome DNA5’mC level. Shock, etc. reported that DNMT1a can locate in the mitochondria through a signal peptide sequence in the N termal of DNMTla peptide sequence and combine with mitochondrial DNA. Beside Mitochondrial DNA encoding proteins involved in electron transfer during mitochondrial oxidative respiratory chain, abnormal mitochondria respiratory complex can lead to the change of mitochondrial biogenesis. Now there is rare research on if DAC can take impact on mitochondrial bigenesis by involving in alter the expression of genes of mitochondrial DNA. The purpose of this study is to investigate whether the DAC can exert influence on mitochondrial function.objective To inverstigate whether Decitabin (DAC) has an effect on the function of mitochondrial biogenesis of synchronized GO/G1cells.Methods MDS-L cells were treated with Aphidicolin (APC) to synchronize cell cycle progress at GO/Gl stage. After treatment of Decitabin at different concentrations (0,5,10,15μmol/L), ROS production were detected by DCFH-DA. Furthermore, qRT-PCR were performed to detect the changes of mitochondrial DNA copy number and of mitochodrial DNA coded genes (ND1、ND6) expressions.Results In comparison with control group, Decitabine, at low concentration (5u mol/L), can promote the production of ROS (P<0.05) and increase the copy number of mtDNA (P<0.05); however, as the concentration increased to15μmol/L, ROS production start to decline even lower than the control (P<0.05). Besides, DAC can significantly change the expression of ND1(NADH dehydrogenase1) and ND6at high concentration.Conclusion Decitabine can affect mitochondrial biogenesis via altering of mtDNA copy number and of genes expression, and these effects seems concentration dependent.