Comprehensive Proteomic Analysis of the Effects of Purine Analogs on Human Raji B-Cell Lymphoma

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BlankComprehensive Proteomic Analysis of the Effects of Purine Analogs on Human

Raji B-Cell Lymphoma.

S Mactier, S Henrich, Y Che, PL Kohnke, and RI son

J Proteome Res, December 23, 2010; .

Cladribine (CdA) and fludarabine (FdAMP) are purine analogs that induce

apoptosis in chronic lymphocytic leukemia and non-Hodgkin's lymphoma, but the

mechanisms are undefined. The effects of CdA and fludarabine nucleoside (FdA) on

the cytosolic, mitochondrial and nuclear proteomes in human Raji lymphoma cells

have been determined using two-dimensional fluorescence difference gel

electrophoresis (DIGE) and mass spectrometry. Differentially abundant proteins

have provided new insights into CdA- and FdA-induced apoptosis. Treatment with

these purine analogs induced changes in proteins involved with intermediary

metabolism, cell growth, signal transduction, protein metabolism and regulation

of nucleic acids. Differentially abundant mitochondrial 39S ribosomal protein

L50, mTERF domain-containing protein 1, chitinase-3 like 2 protein and

ubiquinone biosynthesis protein COQ9, have been identified in cells undergoing

apoptosis. Up-regulation of several stress-associated proteins found in the

endoplasmic reticulum (ER) including GRP78, ERp57 and ORP150 suggests that

purine analog-induced apoptosis may result from ER stress and unfolded protein

response. While mitochondria-dependent apoptosis has been associated with purine

analog cytotoxicity, the likely involvement of the ER stress pathway in CdA- and

FdA-induced apoptosis has been shown here for the first time.

PMID: 21182289