Albumin is a major serum survival factor for renal tubular cells and macrophages through scavenging of ROS

We have previously shown that lysophosphatidic acid (LPA), an abundant seru m lipid that binds with high affinity to albumin, is a potent survival fact or for mouse proximal tubular cells and peritoneal macrophages. We show her e that BSA also has potent survival activity independent of bound lipids. D elipidated BSA (dBSA) protected cells from apoptosis induced by FCS withdra wal at concentrations as low as 1% of that in FCS. dBSA did not activate ph osphatidylinositol 3-kinase, implying that its survival activity occurs via a mechanism distinct from that for most cytokines. On the basis of the fol lowing evidence, we propose that dBSA inhibits apoptosis by scavenging reac tive oxygen species (ROS): 1) FCS withdrawal leads to ROS accumulation that is inhibitable by dBSA; 2) during protection from apoptosis, sulfhydryl an d hydroxyl groups of dBSA are oxidized; and 3) chemical blockage of free su lfhydryl groups or preoxidation of dBSA with H2O2 removes its survival acti vity. Moreover, dBSA confers almost complete protection from cell death in a well-established model of oxidative injury (xanthine/xanthine oxidase). T hese results implicate albumin as a major serum survival factor. Inhibition of apoptosis by albumin occurs through at least two distinct mechanisms: c arriage of LPA and scavenging of ROS.