Metabolic changes induced by DNA damage in Ramos cells: exploring the role of mTORC1 complex

Abstract

DNA damage induces the activation of many different signals associated with repair or cell death, but it is also connected with physiological events, such as adult neurogenesis and B-cell differentiation. DNA damage induces different signaling pathways, some of them linked to important metabolic changes. The mTORC1 pathway has a central role in the regulation of growth processes and cell division in response to environmental changes and also controls protein synthesis, lipid biogenesis, nucleotide synthesis, and expression of glycolytic genes. Here, we report that double-strand breaks induced with etoposide affect the expression of genes encoding different enzymes associated with specific metabolic pathways in Ramos cells. We also analyzed the role of mTOR signaling, demonstrating that doublestrand breaks induce downregulation of mTOR signaling. Specific inhibition of mTORC1 using rapamycin also induced changes in the expression of metabolic genes. Finally, we demonstrated that DNA damage and rapamycin can regulate glucose uptake. In summary, our findings show that etoposide and rapamycin affect the expression of metabolic genes as well as apoptotic and proliferation markers in Ramos cells, increasing our understanding of cancer metabolism. Double-strand breaks (DSB) are considered among the most cytotoxic damage on the DNA, inducing an essential set of molecular mechanisms to prevent and repair these breaks. The DSB induce the DNA damage response (DDR), which promotes cell cycle arrest, DNA repair mechanisms, and even induces apoptosis and cellular senescence [1]. Interestingly, this DNA repair machinery can be induced in different cells in an intentional and calculated way to generate genetic modification with diverse functionalities, such as neural development, and adult neurogenesis. Specifically, in B cells, the DDR induces B-cell differentiation [2,3], Abbreviations 4EBP1, eukaryotic translation initiation factor 4E-binding protein 1; ACSL3, acyl-CoA synthetase for long-chain fatty acids of family 3;