Cantin A M, Paquette B, Richter M, Larivée P
Pulmonary Research Unit, Department of Medicine, and Department of Radiobiology, University of Sherbrooke, Sherbrooke, Quebec, Canada.
Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 1):1539-46. doi: 10.1164/ajrccm.162.4.9910106.
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 NH(4)Cl. The degree to which albumin increased GSH levels was sufficient to protect cells against H(2)O(2)-mediated cytotoxicity and to decrease TNF-alpha-mediated NF-kappaB activation. We conclude that albumin specifically modulates cellular GSH levels, an effect sufficient to protect cells against oxidant injury and regulate NF-kappaB activation.
人血清白蛋白（HSA）是一种富含胱氨酸的血清蛋白，许多细胞通过受体介导的内吞作用和液相内吞作用摄取该蛋白。我们推测HSA可能在调节细胞抗氧化剂氧化还原信号传导中发挥作用。肺上皮细胞（A549）、成纤维细胞（HFL1）和血液淋巴细胞在与HSA孵育8小时后，谷胱甘肽（GSH）水平升高。血浆来源的HSA或重组HSA均观察到类似的GSH升高。去除HSA的血清对细胞GSH没有影响。在体内气道滴注HSA后，正常小鼠肺中也观察到GSH升高。然而，GSH的增强与HSA上的游离半胱氨酸残基（Cys-34）的氧化还原状态无关，不过，HSA中二硫键的还原抑制了细胞GSH的升高。此外，液泡（H(+)）-ATP酶抑制剂巴弗洛霉素A(1)和 concanamycin以及破坏膜pH值的离子载体莫能菌素可抑制白蛋白介导的GSH升高，但20 mM NH(4)Cl则无此作用。白蛋白增加GSH水平的程度足以保护细胞免受H(2)O(2)介导的细胞毒性作用，并降低TNF-α介导的NF-κB激活。我们得出结论，白蛋白特异性调节细胞GSH水平，这种作用足以保护细胞免受氧化损伤并调节NF-κB激活。
