Albumin activates the AKT signaling pathway and protects B-chronic lymphocytic leukemia cells from chlorambucil- and radiation-induced apoptosis.

Content Provider	Semantic Scholar
Author	Ganeshaguru, Kanagasabai Anderson, Robert B. J. Bruckdorfer, Karl Richard Palmqvist, Lars Prentice, Hugh Grant Hoffbrand, Allan Victor Wickremasinghe, Ranmohan Gitendra
Copyright Year	2003
Abstract	Activation of the phosphatidylinositol 3- kinase/AKT pathway antagonizes apoptosis in diverse cellular systems. We previously showed that human plasma activated AKT and potently blocked the ability of chlorambucil or gamma radiation to induce apoptosis of B-chronic lymphocytic leukemia (CLL) cells. Here we report experiments that identify albumin as the major component of plasma that blocks CLL cell killing by chlorambucil or radiation. Intact plasma depleted of albumin by chromatography on Cibacron blue-Sepharose or plasma from a subject with analbuminemia failed either to activate AKT or to protect CLL cells from chlorambucil-induced apoptosis. Both functions were restored by re-addition of albumin. The protective action of albumin as well as AKT activation was compromised by the binding of lipids. Fluorescence-activated cell sorter (FACScan) analysis demonstrated the uptake of fluoresceinated albumin by CLL cells. Accumulation of albumin in intracellular vesicles was also shown by confocal microscopy. Indirect inhibition of AKT activation by the phosphatidylinositol 3-kinase inhibitor LY294002 reversed the blockade of chlorambucil-induced killing by plasma albumin. The data suggest that activation of AKT consequent to binding of albumin by CLL cells blocks chlorambucil- and radiation-induced apoptosis. Strategies designed to block albumin-induced antiapoptotic signaling may, therefore, be of value in enhancing cytotoxic drug action on CLL cells.
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://discovery.ucl.ac.uk/7116/1/7116.pdf
Alternate Webpage(s)	http://eprints.ucl.ac.uk/7116/1/7116.pdf
PubMed reference number	12480711v1
Volume Number	101
Issue Number	8
Journal	Blood
Language	English
Access Restriction	Open
Subject Keyword	1-Phosphatidylinositol 3-Kinase AKT Signaling Pathway Activation action Antiapoptotic Agent Apoptosis Chlorambucil Chronic Lymphocytic Leukemia Fluorescence Gamma Rays LY 294002 Leukemia, B-Cell Lymphoid leukemia Microscopy, Confocal Phosphatidylinositide 3-Kinase Inhibitor Proto-Oncogene Proteins c-akt Signal Transduction Pathways Vesicle (morphologic abnormality) patent blue violet
Content Type	Text
Resource Type	Article