Objective The nucleolar protein PES1(Pescadillo homolog 1)plays critical roles in ribosome biogenesis and cell cycle regulation,yet its involvement in cellular senescence remains poorly understood.This study aimed to ...Objective The nucleolar protein PES1(Pescadillo homolog 1)plays critical roles in ribosome biogenesis and cell cycle regulation,yet its involvement in cellular senescence remains poorly understood.This study aimed to comprehensively investigate the functional consequences of PES1 suppression in cellular senescence and elucidate the molecular mechanisms underlying its regulatory role.Methods Initially,we assessed PES1 expression patterns in two distinct senescence models:replicative senescent mouse embryonic fibroblasts(MEFs)and doxorubicin-induced senescent human hepatocellular carcinoma HepG2 cells.Subsequently,PES1 expression was specifically downregulated using siRNA-mediated knockdown in these cell lines as well as additional relevant cell types.Cellular proliferation and senescence were assessed by EdU incorporation and SA-β-gal staining assays,respectively.The expression of senescence-associated proteins(p53,p21,and Rb)and SASP factors(IL-6,IL-1β,and IL-8)were analyzed by Western blot or qPCR.Furthermore,Northern blot and immunofluorescence were employed to evaluate pre-rRNA processing and nucleolar morphology.Results PES1 expression was significantly downregulated in senescent MEFs and HepG2 cells.PES1 knockdown resulted in decreased EdU-positive cells and increased SA-β-gal-positive cells,indicating proliferation inhibition and senescence induction.Mechanistically,PES1 suppression activated the p53-p21 pathway without affecting Rb expression,while upregulating IL-6,IL-1β,and IL-8 production.Notably,PES1 depletion impaired pre-rRNA maturation and induced nucleolar stress,as evidenced by aberrant nucleolar morphology.Conclusion Our findings demonstrate that PES1 deficiency triggers nucleolar stress and promotes p53-dependent(but Rb-independent)cellular senescence,highlighting its crucial role in maintaining nucleolar homeostasis and regulating senescence-associated pathways.展开更多
为了筛选适宜塞外红苹果冷藏的保鲜袋,研究了在0~0.5℃的贮藏条件下,0.01、0.02、0.04mm厚度的PE(聚乙烯,polyethylene)保鲜袋结合1-甲基环丙烯(1-methylcyclopropene,1-MCP)缓释剂处理对果肉硬度、可溶性固形物含量、可滴定酸含量、外...为了筛选适宜塞外红苹果冷藏的保鲜袋,研究了在0~0.5℃的贮藏条件下,0.01、0.02、0.04mm厚度的PE(聚乙烯,polyethylene)保鲜袋结合1-甲基环丙烯(1-methylcyclopropene,1-MCP)缓释剂处理对果肉硬度、可溶性固形物含量、可滴定酸含量、外观及风味以及原果胶含量、可溶性果胶含量、纤维素含量、乙醇含量、乙醛含量、总抗氧化能力、过氧化氢含量等品质指标的影响。结果表明,与CK相比,不同厚度的保鲜袋结合1-MCP缓释剂处理均能有效延缓塞外红果肉硬度、可溶性固形物含量、可滴定酸含量的下降速度,抑制原果胶含量的降低和可溶性果胶含量的升高,延缓乙醇、乙醛高峰的出现时间,维持果实总抗氧化能力在较高的水平。综合比较认为:0.02 mm PE袋+1-MCP缓释剂和0.01 mm PE袋+1-MCP缓释剂2个处理的贮藏保鲜效果相对较好,贮藏120 d及货架5 d期间,能保持果实较好的硬度、外观及风味,有效延缓果实的衰老;0.04 mm PE保鲜袋贮藏的果实果皮出现褐变,而且果肉有异味,不适宜用于塞外红果实冷藏。展开更多
文摘Objective The nucleolar protein PES1(Pescadillo homolog 1)plays critical roles in ribosome biogenesis and cell cycle regulation,yet its involvement in cellular senescence remains poorly understood.This study aimed to comprehensively investigate the functional consequences of PES1 suppression in cellular senescence and elucidate the molecular mechanisms underlying its regulatory role.Methods Initially,we assessed PES1 expression patterns in two distinct senescence models:replicative senescent mouse embryonic fibroblasts(MEFs)and doxorubicin-induced senescent human hepatocellular carcinoma HepG2 cells.Subsequently,PES1 expression was specifically downregulated using siRNA-mediated knockdown in these cell lines as well as additional relevant cell types.Cellular proliferation and senescence were assessed by EdU incorporation and SA-β-gal staining assays,respectively.The expression of senescence-associated proteins(p53,p21,and Rb)and SASP factors(IL-6,IL-1β,and IL-8)were analyzed by Western blot or qPCR.Furthermore,Northern blot and immunofluorescence were employed to evaluate pre-rRNA processing and nucleolar morphology.Results PES1 expression was significantly downregulated in senescent MEFs and HepG2 cells.PES1 knockdown resulted in decreased EdU-positive cells and increased SA-β-gal-positive cells,indicating proliferation inhibition and senescence induction.Mechanistically,PES1 suppression activated the p53-p21 pathway without affecting Rb expression,while upregulating IL-6,IL-1β,and IL-8 production.Notably,PES1 depletion impaired pre-rRNA maturation and induced nucleolar stress,as evidenced by aberrant nucleolar morphology.Conclusion Our findings demonstrate that PES1 deficiency triggers nucleolar stress and promotes p53-dependent(but Rb-independent)cellular senescence,highlighting its crucial role in maintaining nucleolar homeostasis and regulating senescence-associated pathways.
文摘为了筛选适宜塞外红苹果冷藏的保鲜袋,研究了在0~0.5℃的贮藏条件下,0.01、0.02、0.04mm厚度的PE(聚乙烯,polyethylene)保鲜袋结合1-甲基环丙烯(1-methylcyclopropene,1-MCP)缓释剂处理对果肉硬度、可溶性固形物含量、可滴定酸含量、外观及风味以及原果胶含量、可溶性果胶含量、纤维素含量、乙醇含量、乙醛含量、总抗氧化能力、过氧化氢含量等品质指标的影响。结果表明,与CK相比,不同厚度的保鲜袋结合1-MCP缓释剂处理均能有效延缓塞外红果肉硬度、可溶性固形物含量、可滴定酸含量的下降速度,抑制原果胶含量的降低和可溶性果胶含量的升高,延缓乙醇、乙醛高峰的出现时间,维持果实总抗氧化能力在较高的水平。综合比较认为:0.02 mm PE袋+1-MCP缓释剂和0.01 mm PE袋+1-MCP缓释剂2个处理的贮藏保鲜效果相对较好,贮藏120 d及货架5 d期间,能保持果实较好的硬度、外观及风味,有效延缓果实的衰老;0.04 mm PE保鲜袋贮藏的果实果皮出现褐变,而且果肉有异味,不适宜用于塞外红果实冷藏。
