Ferroptosis, an iron-dependent type of cell death, is being considered for new clinical treatments of malignant tumors that are difficult to treat with apoptosis inducers. Although several reports have attempted to in...Ferroptosis, an iron-dependent type of cell death, is being considered for new clinical treatments of malignant tumors that are difficult to treat with apoptosis inducers. Although several reports have attempted to increase the sensitivity of cells to cell death by combining ferroptosis and apoptosis inducers using a single treatment, detailed elucidation of the respective mechanisms of ferroptosis and apoptosis during cell death remains unclear. Here, we evaluated combined treatment effectiveness using the apoptosis-sensitive rat insulinoma INS-1 cell lines. DNA laddering, an indicator of camptothecin (CPT)-induced apoptosis, was abolished by adding RSL3 and ML-162, but not erastin. We found that when the cells were treated with the apoptosis inducer CPT or the ferroptosis inducer RSL3, respectively, the degree of cytotoxicity observed increased dose-dependently. However, a combined CPT and RSL3 treatment did not show a synergistic decrease in cell viability. Camptothecin did not significantly affect increases in intracellular lipid peroxidation and reactive oxygen species or increases in mitochondrial and cytoplasmic free iron levels that were induced by treatment with RSL3 alone. Moreover, deferoxamine and α-tocopherol were found to inhibit RSL3-induced cytotoxicity but did not protect against CPT or CPT and RSL3-induced cytotoxicity. Finally, the exogenous addition of tert-butyl hydroperoxide inhibited DNA ladder formation that is induced by CPT, while the addition of hydrogen peroxide or ferrous ammonium sulfate had no effect. Taken together, these results suggest that lipid peroxides generated during ferroptosis may suppress cell death induced by apoptotic mechanisms.展开更多
In hypersensitive response(HR),programmed cell death(PCD)is reported as a powerful defense mechanism in plant immune responses to pathogen.However,little is known about the PCD in sys-temic acquired resistance(SAR).Us...In hypersensitive response(HR),programmed cell death(PCD)is reported as a powerful defense mechanism in plant immune responses to pathogen.However,little is known about the PCD in sys-temic acquired resistance(SAR).Using tobacco mosaic virus(TMV)to infect the tomato(Lycopersicon esculentum cv.Jiafen 16)we found that localized TMV-infection could induce cell death in the uninoculated parts of the tomatoes,where the enzyme-linked immunosorbent assay(ELISA)showed no spreading virus.The biological and molecular characterization of this cell death was shown as fol-lowing:chromatin condensed and formed peripheral conglomeration in nuclei;cell nucleus were TUNEL positive labeled;genomic DNA was fragmented and showed DNA laddering;mitochondria and chloroplast were disrupted;tonoplast and plasma membrane were shrunk and degradated.These re-sults suggested that with an absence of TMV spread,the local TMV-infection on certain tomato leaves could induce systemic PCD in the root-tips,stem-apices and uninoculated leaves.The systemic PCD has various initiation and synchronization in such tissues and is distinct in inducement and exhibition from HR-PCD and SAR.展开更多
文摘Ferroptosis, an iron-dependent type of cell death, is being considered for new clinical treatments of malignant tumors that are difficult to treat with apoptosis inducers. Although several reports have attempted to increase the sensitivity of cells to cell death by combining ferroptosis and apoptosis inducers using a single treatment, detailed elucidation of the respective mechanisms of ferroptosis and apoptosis during cell death remains unclear. Here, we evaluated combined treatment effectiveness using the apoptosis-sensitive rat insulinoma INS-1 cell lines. DNA laddering, an indicator of camptothecin (CPT)-induced apoptosis, was abolished by adding RSL3 and ML-162, but not erastin. We found that when the cells were treated with the apoptosis inducer CPT or the ferroptosis inducer RSL3, respectively, the degree of cytotoxicity observed increased dose-dependently. However, a combined CPT and RSL3 treatment did not show a synergistic decrease in cell viability. Camptothecin did not significantly affect increases in intracellular lipid peroxidation and reactive oxygen species or increases in mitochondrial and cytoplasmic free iron levels that were induced by treatment with RSL3 alone. Moreover, deferoxamine and α-tocopherol were found to inhibit RSL3-induced cytotoxicity but did not protect against CPT or CPT and RSL3-induced cytotoxicity. Finally, the exogenous addition of tert-butyl hydroperoxide inhibited DNA ladder formation that is induced by CPT, while the addition of hydrogen peroxide or ferrous ammonium sulfate had no effect. Taken together, these results suggest that lipid peroxides generated during ferroptosis may suppress cell death induced by apoptotic mechanisms.
基金the National Natural Science Foundation of China(Grant No.30370084)
文摘In hypersensitive response(HR),programmed cell death(PCD)is reported as a powerful defense mechanism in plant immune responses to pathogen.However,little is known about the PCD in sys-temic acquired resistance(SAR).Using tobacco mosaic virus(TMV)to infect the tomato(Lycopersicon esculentum cv.Jiafen 16)we found that localized TMV-infection could induce cell death in the uninoculated parts of the tomatoes,where the enzyme-linked immunosorbent assay(ELISA)showed no spreading virus.The biological and molecular characterization of this cell death was shown as fol-lowing:chromatin condensed and formed peripheral conglomeration in nuclei;cell nucleus were TUNEL positive labeled;genomic DNA was fragmented and showed DNA laddering;mitochondria and chloroplast were disrupted;tonoplast and plasma membrane were shrunk and degradated.These re-sults suggested that with an absence of TMV spread,the local TMV-infection on certain tomato leaves could induce systemic PCD in the root-tips,stem-apices and uninoculated leaves.The systemic PCD has various initiation and synchronization in such tissues and is distinct in inducement and exhibition from HR-PCD and SAR.
