KU [formula omitted] lupus autoantigen is the transcription factor induced by interleukins (IL)-13 and IL-4 leading to induction of 15-lipoxygenase-1 (15-LO) in human cells

Abstract

Non-homologous end joining (NHEJ) is the major pathway for removing DNA double strand breaks lesions. NHEJ is considered to be a resistant factor against chemotherapy induced neuropathy. β-Lapachone (β-Lap) is one of the antineoplastic agents which is shown to have anti neuroinflammatory effects. Extremely low frequency (<300 Hz) electromagnetic field (EMF) is shown to decrease NHEJ genes expression. Morphine (Mor) is associated with reducing effect on DNA repair and induce DNA damages. The goal of this study was to evaluate the effect of combination treatment of β-Lap, morphine (Mor) and EMF on expression of NHEJ related genes (XRCC4, Ku70, Ku80, DNA-PKcs and LIG4).SH-SY5Y cells (epithelial neuroblasts) were treated with four combinational treatments of β-Lap (2.0 and 3.2 μM), Mor (5.0 μM) and EMF (50 Hz, 0.50 mT, “15 min field on/15 min field off”) and mRNA levels of XRCC4, Ku70, Ku80, DNA-PKcs and LIG4 were evaluated by quantitative real-time PCR and primers specific for the examined genes. The experiments were done in triplicates.No significant alteration in the mRNA levels of NHEJ related genes was observed in “β-Lap alone” and “β-Lap + Mor” treated cells. The expression levels of NHEJ related genes were significantly increased in “β-Lap + EMF” and “β-Lap + Mor + EMF”. Multiple linear regression analysis showed that the effect of EMF and Mor on NHEJ related genes expression is opposite to the effect of β-Lap.In overall, combination of β-Lap, Mor and EMF leads to increased expression of NHEJ related gene expression. This effect may lead to decreased sensitivity of SH-SY5Y cells against β-Lap and can improve its neuroprotective property which might be hopeful for its clinical applications.