Studies on the chaperone protein α-hemoglobin stabilizing protein （AHSP） reveal that abundant AHSP in erythroid cells en-hance the cells＇ tolerance to oxidative stress imposed by excess a-hemoglobin in pathologica...Studies on the chaperone protein α-hemoglobin stabilizing protein （AHSP） reveal that abundant AHSP in erythroid cells en-hance the cells＇ tolerance to oxidative stress imposed by excess a-hemoglobin in pathological conditions. However, the poten-tial intracellular modulation of AHSP expression itself in response to oxidative stress is still unknown. The present study ex-amined the effect and molecular mechanism of STAT3, an oxidative regulator, on the expression of AHSP. AHSP expression increased in K562 cells upon cytokine IL-6-induced STAT3 activation and decreased in STAT3 knock-down K562 cells. Reg-ulation of AHSP in oxidative circumstance was then examined in α-globin-overloaded K562 cells, and real-time PCR showed strengthened expression of both AHSP and STAT3. ChIP analysis showed binding of STAT3 to AHSP promoter and binding was significantly augmented with IL6 stimulation and upon α-globin overexpression. Dual luciferase reporter assays of the wildtype and mutated SB3 element, an IL-6RE site, in the AHSP promoter in K562 cells highlighted the direct regulatory ef-fect of STAT3 on AHSP gene. Finally, direct binding of STAT3 to SB3 site of AHSP promoter was confirmed with EMSA as-says. Our work reveals an adaptive AHSP regulation mediated by the redox-sensitive STAT3 signaling pathway, and provides clues to the therapeutic strategy for AHSP enhancement.展开更多
腹型过敏性紫癜(abdominal type of Henoch-Sch nlein purpura,AHSP)是一种由IgA介导的全身性血管炎,常发于儿童。AHSP由于症状非典型,故早期筛查诊断难度较大,常规通过胃肠镜检查确诊。钙卫蛋白由S100A8和S100A9蛋白亚体组成,一般来源...腹型过敏性紫癜(abdominal type of Henoch-Sch nlein purpura,AHSP)是一种由IgA介导的全身性血管炎,常发于儿童。AHSP由于症状非典型,故早期筛查诊断难度较大,常规通过胃肠镜检查确诊。钙卫蛋白由S100A8和S100A9蛋白亚体组成,一般来源于中性粒细胞,具有多种生物学作用。粪钙卫蛋白浓度与肠道炎症相关,用于评估胃肠道炎症。鉴于AHSP常伴胃肠道疾病,粪钙卫蛋白具备作为AHSP早期诊断指标的潜力。本研究综述了粪钙卫蛋白在AHSP早期诊断中的应用价值,旨在为将其作为AHSP的临床诊断指标增加理论依据。展开更多
基金supported by the National Natural Science Foundation of China(31030026,31021091)the National Basic Research Program of China(2011CB965203,2011CB964803)
文摘Studies on the chaperone protein α-hemoglobin stabilizing protein （AHSP） reveal that abundant AHSP in erythroid cells en-hance the cells＇ tolerance to oxidative stress imposed by excess a-hemoglobin in pathological conditions. However, the poten-tial intracellular modulation of AHSP expression itself in response to oxidative stress is still unknown. The present study ex-amined the effect and molecular mechanism of STAT3, an oxidative regulator, on the expression of AHSP. AHSP expression increased in K562 cells upon cytokine IL-6-induced STAT3 activation and decreased in STAT3 knock-down K562 cells. Reg-ulation of AHSP in oxidative circumstance was then examined in α-globin-overloaded K562 cells, and real-time PCR showed strengthened expression of both AHSP and STAT3. ChIP analysis showed binding of STAT3 to AHSP promoter and binding was significantly augmented with IL6 stimulation and upon α-globin overexpression. Dual luciferase reporter assays of the wildtype and mutated SB3 element, an IL-6RE site, in the AHSP promoter in K562 cells highlighted the direct regulatory ef-fect of STAT3 on AHSP gene. Finally, direct binding of STAT3 to SB3 site of AHSP promoter was confirmed with EMSA as-says. Our work reveals an adaptive AHSP regulation mediated by the redox-sensitive STAT3 signaling pathway, and provides clues to the therapeutic strategy for AHSP enhancement.
文摘腹型过敏性紫癜(abdominal type of Henoch-Sch nlein purpura,AHSP)是一种由IgA介导的全身性血管炎,常发于儿童。AHSP由于症状非典型,故早期筛查诊断难度较大,常规通过胃肠镜检查确诊。钙卫蛋白由S100A8和S100A9蛋白亚体组成,一般来源于中性粒细胞,具有多种生物学作用。粪钙卫蛋白浓度与肠道炎症相关,用于评估胃肠道炎症。鉴于AHSP常伴胃肠道疾病,粪钙卫蛋白具备作为AHSP早期诊断指标的潜力。本研究综述了粪钙卫蛋白在AHSP早期诊断中的应用价值,旨在为将其作为AHSP的临床诊断指标增加理论依据。
