Does loss of glutathione homeostasis associated with neuronal senescence facilitate TRPM2 channel activation in cultured hippocampal pyramidal neurons?
These results indicate that GSH plays a physiologically relevant role in the regulation of TRPM2 currents in hippocampal pyramidal neurons. This interaction may play an important role in aging and neurological diseases associated with depletion of GSH.
The functional redundancy of MMR and DNA glycosylases in FU processing should ensure that the drug is efficiently removed from DNA before it can interfere with essential DNA metabolic processes, such as transcription. However, in FU-treated cells, the nucleotide pools are depleted of thymine. The repair synthesis might thus be inhibited and leave cytotoxic gaps or breaks in DNA. Moreover, FU and/or 5-fluorouracil-2'-deoxyuridine-5'-triphosphate removed from DNA will increase the intracellular concentration of the drug and thus exacerbate its cytotoxicity.