B Cell Responses to Oxidative Stress

Author(s): Yumi Tohyama, Tomoko Takano, Hirohei Yamamura

Journal Name: Current Pharmaceutical Design

Volume 10 , Issue 8 , 2004

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Abstract:

B-lymphocytes are exposed to a reduction / oxidation environment during activation or inflammatory process, and the antioxidant systems are functional to protect themselves against harmful reactive oxygen species (ROS). The crucial roles of thioredoxin-2 (Trx-2) and a DNA repair enzyme APE / Ref-1 in mitochondria are reported in B-lymphocytes. Furthermore, ROS stimulate different signaling pathways in many cellular responses. Their effects often cause some diseases or are utilized for the treatment of other diseases. For example, the cells derived from Fanconi anemia (FA) patients are intolerant of oxidative stress and the therapeutic effect of anti-CD20 monoclonal antibody rituximab on B cell lymphoproliferative disorders is due to the generation of ROS. To clarify the oxidative stress-induced signaling pathways, we stimulated a B cell line with various concentrations of H2 O2 . As a result, a protein tyrosine kinase, Syk was involved in the induction of G2 / M arrest and protection of cells from apoptosis. Syk might inhibit the activation of caspase-9 through Akt thereby protecting cells from oxidative stress-induced apoptosis. On the other hand, Syk-dependent PLC-γ2 activation was required for acceleration towards apoptosis following oxidative stress. These findings suggest that oxidative stress-induced Syk activation triggers the activation of different pathways, such as pro-apoptotic or survival pathways, and that the balance of these pathways is a key factor in determining the fate of the cells exposed to oxidative stress. In contrast, the stimulation with the millimolar concentrations of H2 O2 rapidly led to necrosis in which tyrosine phosphorylation of FAK was involved at the downstream of Lyn and Syk.

Keywords: reactive oxygen species (ros), apoptosis, necrosis, cell cycle arrest, protein tyrosine kinase, syk

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Article Details

VOLUME: 10
ISSUE: 8
Year: 2004
Page: [835 - 839]
Pages: 5
DOI: 10.2174/1381612043452947
Price: $65

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