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Proteolysis
in the Myelopathy of Acquired Immunodeficiency Syndrome: Preferential Loss
of the C-8 Component of Myelin Basic Protein |
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Dwayne A. Wolf,
Shailaja R. Dholakia, Michael J. Keherly, Monica G. RodrAaiguez-Wolf, Miles
W. Cloyd, and Benjamin B. Gelman |
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Departments
of Pathology (DAW, BBG, SRD, MGR, MWC), Anatomy and Neurosciences (BBG),
Surgery (MJK), and Microbiology (MWC), University of Texas Medical Branch,
Galveston, Texas |
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Many patients with AIDS
have a myelopathy characterized by vacuolization of spinal cord white matter.
The biochemical and molecular changes underlying this myelin disturbance
have not yet been characterized. Myelin basic protein (MBP) is potentially
important because it is a key structural protein of myelin with roles in
compaction and stabilization. In the present study, we describe the steady-state
protein concentration of MBP in 46 patients with AIDS and 12 control subjects
at autopsy. Patients with myelopathy exhibited no change in the abundance
of the predominant 18.5- and 17.2-kd isoforms, but a 14-kd MBP-immunoreactive
degradation fragment was increased significantly. MBP degradation correlated
significantly with the severity of histopathologic changes, including neutral
lipid deposition, the density of vacuolated fibers, and the number of ferritin-stained
activated microglia. Alkaline gel electrophoresis of isolated MBP showed
preferential loss of the least cationic isomer (C-8). The concentration
of MBP RNA in slot blots was normal in cords exhibiting myelopathy, and
the ratio of mRNA corresponding to the 18.5- and 17.2-kd MBP isoforms, measured
using reverse transcriptase-PCR, was not altered. This study suggests that
mononuclear phagocyte-mediated degradation of MBP may play a role in AIDS
myelopathy, and the preferential loss of the C-8 component of MBP may have
mechanistic implications. |
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