Albumin-mediated regulation of cellular glutathione and nuclear factor kappa B activation
Albumin-mediated regulation of cellular glutathione and nuclear factor kappa B activation
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DOI：
10.1164/ajrccm.162.4.9910106
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发表时间：
2000-10-01
影响因子：
24.7
通讯作者：
Larivée, P
中科院分区：
文献类型：
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作者：
Cantin, AM;Paquette, B;Larivée, P
人血清白蛋白(HSA)是一种富含半胱氨酸的血清蛋白，通过受体介导的液相内吞作用被许多细胞摄取。我们推测HSA可能在调节细胞抗氧化剂氧化还原信号方面发挥作用。肺上皮细胞(A549)、成纤维细胞(HFL1)和血淋巴细胞在与HSA孵育8h后谷胱甘肽(GSH)水平升高。血浆来源的或重组人血清白蛋白也观察到类似的GSH升高。去除HSA的血清对细胞内GSH无影响。正常小鼠肺内滴入人血清白蛋白后，GSH也升高。GSH升高与HSA上游离半胱氨酸残基(Cys-34)的氧化还原状态无关，但HSA上二硫键的减少抑制了细胞内GSH的升高。此外，白蛋白介导的GSH升高可被空泡型(H+)-ATPase抑制剂巴菲霉素A(1)和刀豆素以及膜pH干扰的离子载体Monensin所抑制，但不能被20 mM NH4Cl所抑制。白蛋白增加谷胱甘肽水平的程度足以保护细胞免受过氧化氢介导的细胞毒性，并降低肿瘤坏死因子-α介导的核因子-kappaB的激活。我们得出结论，白蛋白特异性地调节细胞GSH水平，这种作用足以保护细胞免受氧化性损伤，并调节核因子-kappaB的激活。
Human serum albumin (HSA) is a cystine-rich serum protein taken up by many cells through receptor-mediated and fluid-phase endocytosis. We hypothesized that HSA may play a role in modulating cellular antioxidant redox signaling. Lung epithelial cells (A549), fibroblasts (HFL1), and blood lymphocytes had increased glutathione (GSH) levels after 8 h incubation with HSA. Similar GSH increases were observed with either plasma-derived or recombinant HSA. Serum depleted of HSA had no effect on cellular GSH. The GSH increase was also observed in normal murine lungs upon in vivo airway instillation of HSA. GSH enhancement was not related to the redox state of the free cysteine residue (Cys-34) on HSA, however, reduction of disulfide bonds in HSA inhibited the increase in cellular GSH. In addition, the albumin-mediated increase in GSH was inhibited by the vacuolar (H+)-ATPase inhibitors, bafilomycin A(1) and concanamycin, as well as by the membrane pH-disrupting ionophore monensin, but not by 20 mM NH4Cl. The degree to which albumin increased GSH levels was sufficient to protect cells against H2O2-mediated cytotoxicity and to decrease TNF-alpha-mediated NF-kappa B activation. We conclude that albumin specifically modulates cellular GSH levels, an effect sufficient to protect cells against oxidant injury and regulate NF-kappa B activation.