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KMID : 0948320070070010013
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Konyang Medical Journal
2007 Volume.7 No. 1 p.13 ~ p.17
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Expression Patton of Stress Proteins Induced by Immunosuppressante, Cyclosporin A
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Mok Woo-Kyun
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Abstract
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Background: Immunosuppressive agent of cyclosporin A (CsA) is commonly used in transplantation of organs to
avoid the rejection as well as to treat autoimmune disease. In the cell, CsA is banded the intracellular protein called
cyclophilin (CyP) which has enzyme activity of peptidyl-prolyl cis-trans isomerase (PPI) and molecular chaperone
function. The CsA-CyP complex has a specific inhibitory effect on the calmodulin-dependent protein phosphatase
calcineurin, which leads to the inhibition of the T lymphocyte activation. The mechanisms of the loss of CsA activation
by cyclophilin remain unclear. In this mind, this study is to use CsA to approach the physiological significance
of the PPI activities in the cell. If PPIs are essential for the protein folding, their inhibition by CsA ought to lead to the accumulation of denatured proteins in the cells. These denatured proteins would increase the level of the stress response and the subsequent synthesis of heat shock proteins (HSPs). Therefore I decided to look at the effects of CsA on the synthesis of HSPs in the CsA and heat-shock treated cells by both methods SDS-PAGE for ability of total protein synthesis and Western blotting to detect alternative HSPs synthesis using anti-HSP antibodies.
Results: 1. In SDS-PAGE analysis experiment, no total protein changes are detected in case of only CsA used as
well as only heat treated to the cells. 2. By Western blotting analysis, both kind of stress proteins, HSP 70 and HSP
90 of cytosol resident stress proteins, and ER resident stress protein of Grp 94, are constantly expressed with or without
CsA, however expression of another ER stress protein of ERp 72 is increased by CsA dose dependently, especially
its high expression is detected on low concentration (2, 6 μM) of CsA.
Conclusion: According to the results above, it has demonstrated that CsA alone does not induce alternated protein synthesis in the cells, however which inhibits PPIase in the condition of denatured proteins are accumulated in the
cells. Its localization is not in the cytosol but in the ER of the cells. Especially ERp 72 called intracellular scavenger
is increased its expression against denatured proteins in the ER and CsA.
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KEYWORD
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Cyclosporine A, Heat Shock Protein
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