Albumin is a major serum survival factor for murine renal proximal
tubular cells and macrophages that acts by scavenging reactive oxygen
species.
Iglesias, Jos[acute]e, Vivian Elizabeth Abernethy, Zhiyong Wang,
Wilfred Lieberthal, Jason S. Koh and Jerrold S. Levine.
1Renal Section, Department of Medicine, Boston University School of
Medicine, Boston, Massachusetts, 02118, USA
APStracts 6:0125F, 1999.
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% that in FCS. dBSA did not activate PI3K, implying that its
survival activity occurs via a mechanism distinct from that for most
cytokines. Based on the following evidence, we propose that dBSA
inhibits apoptosis by scavenging reactive oxygen species (ROS): i)
FCS withdrawal leads to ROS accumulation that is inhibitable by dBSA;
ii) during protection from apoptosis, sulfhydryl and hydroxyl groups
of dBSA are oxidized; iii) chemically blocking free sulfhydryl groups
or pre-oxidation of dBSA with H2O2 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.
Received 4 March 1999; accepted in final form 15 June 1999.
APS Manuscript Number F059-9.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 25 June 1999