Dictyostelium discoideum, a unicellular eukaryote, exhibits multicellularity upon nutrient starvation and is a good model system for developmental studies, and for the study of various signal transduction pathways. Reactive oxygen species at low doses act as signaling molecules; however, at high doses they are known to cause DNA damage that results in the activation of poly(ADP‐ribose) polymerase (PARP). We have earlier reported the high resistance of the unicellular stage of D. discoideum to oxidative stress, and we now show the response of this organism to oxidative stress and the role of PARP during development. We used hydroxylamine (HA) to induce in situ generation of H2O2 and monitored the effect of benzamide, a PARP inhibitor, on oxidative stress‐induced changes in D. discoideum development. Interestingly, oxidative stress resulted in PARP activation within 5 min that was inhibited by benzamide. Oxidative stress‐induced delay in developmental pattern was also partially restored by benzamide. We studied the long‐term effects of PARP inhibition under oxidative stress, and our results demonstrated that spores formed under HA stress exhibited significant delay in germination in comparison to benzamide‐pretreated HA‐stressed cells. However, second‐generation cells showed normal development, signifying that PARP inhibition has no deleterious effect on D. discoideum development under oxidative stress.
Resveratrol (R), a plant polyphenol, is known to reduce Cu (II) to Cu (I) generating reactive oxygen species that can cleave plasmid DNA. Here we report a surprising observation of a paradoxical synergistic effect between R and Cu whereby plasmid DNA cleaving / degrading activity of R-Cu increased progressively as the ratio of R to Cu was increased i.e., the concentration of Cu was successively reduced with respect to a fixed concentration R. Whereas cleavage of plasmid DNA occurred at low molar ratios of R to Cu, at higher ratios, complete degradation of DNA was achieved. By further increasing the ratio, whereby the concentration of Cu was reduced to very low levels, the DNA degrading activity of R-Cu was lost. This paradoxical synergistic effect is also seen with respect to eukaryotic genomic DNA and RNA. Since R-Cu may have anti-cancer and anti-viral activities, our findings may not only help to improve the therapeutic efficacy of R-Cu but also reduce its toxic side effects with the use of low concentration of Cu.
Resveratrol (R), a plant polyphenol, is known to reduce Cu (II) to Cu (I) generating reactive oxygen species that can cleave plasmid DNA. Here we report a surprising observation of a paradoxical relationship between R and Cu whereby plasmid DNA cleaving / degrading activity of R-Cu increased progressively as the ratio of R to Cu was increased i.e., the concentration of Cu was successively reduced with respect to a fixed concentration R. Whereas cleavage of plasmid DNA occurred at low molar ratios of R to Cu, at higher ratios, complete degradation of DNA was achieved. By further increasing the ratio, whereby the concentration of Cu was reduced to very low levels, the DNA degrading activity of R-Cu was lost. This paradoxical relationship is also seen with respect to eukaryotic genomic DNA and RNA. Since R-Cu may have anti-cancer and anti-viral activities, our findings may not only help to improve the therapeutic efficacy of R-Cu but also reduce its toxic side effects with the use of low concentration of Cu.
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