Physarum polycephalum L., a naturally synchronized myxomycophyta, was demonstrated to contain a cyclin B1-like protein by Western blot and immunoelectron microscopy. The content and subcellular location of the protein...Physarum polycephalum L., a naturally synchronized myxomycophyta, was demonstrated to contain a cyclin B1-like protein by Western blot and immunoelectron microscopy. The content and subcellular location of the protein varied during the cell cycle. The cyclin B1-like protein was first detected in the plasmodia of S phase while it did not appear in the nuclei until late G2 phase. The content of the protein in both the plasmodia and nuclei rose gradually onwards, peaked at metaphase and disappeared abruptly at ana-telophase. The protein was found to be distributed in both the cytoplasm and nuclei in late G2 phase and metaphase. In nuclei, the protein was mainly located in the chromosomal and nucleolar areas. The results suggest that the cyclin B1-like protein of P. polycephalum begins to be synthesized at S phase, enters the nuclei at late G2 phase, accumulates in both cytoplasm and nuclei onwards and breaks down at ana-telophase. The results also suggest that the cyclin B1-like protein acts as a cytoplasmic-nuclear protein during certain phases of the cell cycle.展开更多
Objectives:Glioblastoma(GBM)is a prevalent malignant brain tumor prone to drug resistance.We previously found a strong correlation between SH3 domain GRB2-like endophilin B1(SH3GLB1)and superoxide dismutase 2(SOD2),wh...Objectives:Glioblastoma(GBM)is a prevalent malignant brain tumor prone to drug resistance.We previously found a strong correlation between SH3 domain GRB2-like endophilin B1(SH3GLB1)and superoxide dismutase 2(SOD2),which converts O_(2) to hydrogen peroxide(H_(2)O_(2)).Prior studies show that H_(2)O_(2) redox signaling is vital for physiological processes and can drive tumor progression.Therefore,we aim to define how H_(2)O_(2) signaling regulates SH3GLB1 and AKT(protein kinase B)pathways in GBM and to assess whether modulating H_(2)O_(2) reverses temozolomide(TMZ)resistance.Methods:We used cultured cells and pharmacological inhibitors and activators to confirm the significance of H_(2)O_(2) signaling.GBM cells were used to verify the role of H_(2)O_(2) signaling in cell state transitions and animal experiments identified optimal treatment strategies.Results:We found that SOD2 acts as an upstream regulator of SH3GLB1.When SOD inhibitors and TMZ were combined,cells showed reduced SH3GLB1 and autophagy levels.SH3GLB1 was found to be regulated by H_(2)O_(2) via AKT signaling using redox homeostasis-regulating experiments.Although treatment-induced changes in mitochondrial H_(2)O_(2) levels mirrored those in the cytosol,parental and resistant cells exhibited divergent fates,highlighting cell-fate plasticity.TMZ combined with a redox modulator reduced resistant tumor cell growth(about 2/3 reduction of tumor size;p<0.05)and suppressed SH3GLB1 and autophagy levels in animal models.The TMZ-induced increase in SH3GLB1 expression was reversed by HgCl2,which inhibited the aquaporin-9/AKT signaling.Conclusion:Overall,these findings underscore the importance of H_(2)O_(2)-SH3GLB1 signaling in GBM and may inform future therapeutic strategies for overcoming TMZ resistance.展开更多
文摘Physarum polycephalum L., a naturally synchronized myxomycophyta, was demonstrated to contain a cyclin B1-like protein by Western blot and immunoelectron microscopy. The content and subcellular location of the protein varied during the cell cycle. The cyclin B1-like protein was first detected in the plasmodia of S phase while it did not appear in the nuclei until late G2 phase. The content of the protein in both the plasmodia and nuclei rose gradually onwards, peaked at metaphase and disappeared abruptly at ana-telophase. The protein was found to be distributed in both the cytoplasm and nuclei in late G2 phase and metaphase. In nuclei, the protein was mainly located in the chromosomal and nucleolar areas. The results suggest that the cyclin B1-like protein of P. polycephalum begins to be synthesized at S phase, enters the nuclei at late G2 phase, accumulates in both cytoplasm and nuclei onwards and breaks down at ana-telophase. The results also suggest that the cyclin B1-like protein acts as a cytoplasmic-nuclear protein during certain phases of the cell cycle.
基金supported by research grants from the Ministry of Science and Technology(MOST 108-2314-B-400-026 and 109-2013-B-400-036)National Science and Technology Council(NSTC 112-2320-B-214-010 and 113-2320-B-214-002)+1 种基金I-Shou University(ISU-112-01-12A,ISU112-S-02 and ISU114-S-04)National Health Research Institutes,Taiwan(CA-111-PP-19).
文摘Objectives:Glioblastoma(GBM)is a prevalent malignant brain tumor prone to drug resistance.We previously found a strong correlation between SH3 domain GRB2-like endophilin B1(SH3GLB1)and superoxide dismutase 2(SOD2),which converts O_(2) to hydrogen peroxide(H_(2)O_(2)).Prior studies show that H_(2)O_(2) redox signaling is vital for physiological processes and can drive tumor progression.Therefore,we aim to define how H_(2)O_(2) signaling regulates SH3GLB1 and AKT(protein kinase B)pathways in GBM and to assess whether modulating H_(2)O_(2) reverses temozolomide(TMZ)resistance.Methods:We used cultured cells and pharmacological inhibitors and activators to confirm the significance of H_(2)O_(2) signaling.GBM cells were used to verify the role of H_(2)O_(2) signaling in cell state transitions and animal experiments identified optimal treatment strategies.Results:We found that SOD2 acts as an upstream regulator of SH3GLB1.When SOD inhibitors and TMZ were combined,cells showed reduced SH3GLB1 and autophagy levels.SH3GLB1 was found to be regulated by H_(2)O_(2) via AKT signaling using redox homeostasis-regulating experiments.Although treatment-induced changes in mitochondrial H_(2)O_(2) levels mirrored those in the cytosol,parental and resistant cells exhibited divergent fates,highlighting cell-fate plasticity.TMZ combined with a redox modulator reduced resistant tumor cell growth(about 2/3 reduction of tumor size;p<0.05)and suppressed SH3GLB1 and autophagy levels in animal models.The TMZ-induced increase in SH3GLB1 expression was reversed by HgCl2,which inhibited the aquaporin-9/AKT signaling.Conclusion:Overall,these findings underscore the importance of H_(2)O_(2)-SH3GLB1 signaling in GBM and may inform future therapeutic strategies for overcoming TMZ resistance.
