ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: Activation of inflammatory and cytotoxic complement effectors that include the C5b-9 complex plays an important pathogenic role in myasthenia gravis, an inflammatory autoimmune disease of the muscle. Altered muscle-specific gene expression has been observed in experimental myasthenic rats. In this study, we have examined the effect of sublytic C5b-9 on myotubes differentiated from C2C12 myoblasts, by generating C5b-9 with C7-deficient serum with or without C7. Within 2 h, C7-deficient serum plus C7, compared with C7-deficient serum alone, induced markedly decreased levels of mRNAs encoding α-actin, troponin I slow twitch isoform, acetylcholine receptor α, and muscle aldolase A, whereas the heat shock protein 83 mRNA level remained constant, by northern analysis. Because the half-life of the acetylcholine receptor α was estimated to be 〉8 h, the C5b-9 effect was, in part, due to enhanced mRNA decay. Because C5b-9 also induced c-jun mRNA and reduced the myoD mRNA level, a possible inhibition of muscle gene transcription by C5b-9 was examined in myotubes transfected with troponin promoter-luciferase gene constructs. Luciferase activity was reduced to 50% in response to C5b-9 at 2 h. Thus, C5b-9 appears to inhibit the muscle-specific gene expression by stimulating mRNA decay and by decreasing the transcription process. The data also indicate a possible pathogenic role of C5b-9 in immune-mediated inflammatory muscle disorders in which complement activation has been implicated.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.1997.68041581.x
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