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 serum lipid that binds with high affinity to albumin, is a potent survival factor for mouse proximal tubular cells and peritoneal macrophages. We show here that BSA also has potent survival activity independent of bound lipids. Delipidated BSA (dBSA) protected cells from apoptosis induced by FCS withdrawal at concentrations as low as 1% of that in FCS. dBSA did not activate phosphatidylinositol 3-kinase, implying that its survival activity occurs via a mechanism distinct from that for most cytokines. On the basis of the following evidence, we propose that dBSA inhibits apoptosis by scavenging reactive oxygen species (ROS): 1) FCS withdrawal leads to ROS accumulation that is inhibitable by dBSA; 2) during protection from apoptosis, sulfhydryl and hydroxyl groups of dBSA are oxidized; and 3) chemical blockage of free sulfhydryl groups or preoxidation of dBSA with H(2)O(2) removes its survival activity. Moreover, dBSA confers almost complete protection from cell death in a well-established model of oxidative injury (xanthine/xanthine oxidase). These results implicate albumin as a major serum survival factor. Inhibition of apoptosis by albumin occurs through at least two distinct mechanisms: carriage of LPA and scavenging of ROS.
Iglesias
J
J
Renal Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Abernethy
V E
VE
Wang
Z
Z
Lieberthal
W
W
Koh
J S
JS
Levine
J S
JS
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004340:Drug Contamination; D004789:Enzyme Activation / Q000502:physiology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000494:pharmacology; D009997:Osmotic Pressure; D010084:Oxidation-Reduction; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000037:antagonists & inhibitors / Q000378:metabolism
D000975:Antioxidants; D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D008934:Mitogens; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D012710:Serum Albumin, Bovine; D019869:Phosphatidylinositol 3-Kinases