Protein phosphatase 2A modulates the proliferation of human multiple myeloma cells via regulation of the production of reactive oxygen intermediates and anti-apoptotic factors

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Title
Protein phosphatase 2A modulates the proliferation of human multiple myeloma cells via regulation of the production of reactive oxygen intermediates and anti-apoptotic factors
Author(s)
Hyung Sik Kang; In Pyo Choi
Bibliographic Citation
Cellular Immunology, vol. 213, no. 1, pp. 34-44
Publication Year
2001
Abstract
To understand the roles of reactive oxygen intermediates (ROI) in Fas-mediated apoptosis of myeloma cells, the effects of antioxidants were tested. Fas-mediated apoptosis was further increased in the presence of antioxidants such as N-acetyl-L-cysteine and glutathione, but it was decreased when hydrogen peroxide was added. The intracellular ROI level was significantly decreased in myeloma cells treated with okadaic acid, an inhibitor of protein phosphatases 1 and 2A (PP1/PP2A). To clarify the direct roles of PP2A in myeloma cell growth, the PP2A transfected cell lines, sense- or antisense-PP2A transfectants, were established. Spontaneous cell growth of antisense-PP2A transfectants was reduced compared with that of vector transfectants. The intracellular ROI level was significantly decreased in antisense-PP2A transfectants but increased in sense-PP2A transfectants compared with vector controls. In addition, anti-apoptotic factors such as bcl-2 and IL-6 were reduced in antisense-PP2A transfectants. Taken together, these results indicate that PP2A is an essential factor for survival and growth of myeloma cells via regulation of intracellular ROI and anti-apoptotic factors.
Keyword
Apoptosisbcl-2IL-6myelomaPP2AROI
ISSN
0008-8749
Publisher
Elsevier
DOI
http://dx.doi.org/10.1006/cimm.2001.1861
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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