Related Experiment Videos
Hydrolysis of myelin basic protein in human myelin by terminal complement complexes
1Department of Pathology, University of Maryland School of Medicine, Baltimore 21201.
The Journal of Biological Chemistry
|May 25, 1988
Summary
Terminal complement complexes (TCC) activate proteases in myelin, leading to myelin basic protein (BP) hydrolysis. This process, particularly at the C5b6-8 stage, may contribute to demyelinating diseases.
Area of Science:
- Neuroimmunology
- Complement system biology
- Demyelinating diseases research
Background:
- Terminal complement complexes (TCC) are implicated in demyelination.
- TCC influences membrane-associated enzymes and intracellular calcium (Ca2+).
Purpose of the Study:
- To investigate if TCC activates Ca2+-dependent neutral proteases in myelin.
- To determine if activated proteases hydrolyze myelin basic protein (BP).
Main Methods:
- Incubation of sealed myelin vesicles with antibodies and complement components (C7-deficient serum, C7).
- Assessing myelin basic protein (BP) hydrolysis at different stages of complement complex assembly (C5b6,7; C5b6-8; C5b6-9).
- Evaluating the Ca2+ dependence of BP hydrolysis.
Main Results:
- Significant BP hydrolysis was observed with C5b6,7 assembly, increasing at the C5b6-8 stage.
- C5b6-9 formation did not further enhance BP hydrolysis compared to C5b6-8.
- BP hydrolysis by C5b6,7 was Ca2+-independent, while C5b6-8/C5b6-9 hydrolysis was partially Ca2+-dependent.
Conclusions:
- TCC formation on myelin membranes likely activates associated neutral proteases.
- Complement peptide insertion and channel formation by TCC may lead to BP hydrolysis.
- This mechanism could alter myelin structure and exacerbate inflammatory demyelination.