Proteolysis in the myelopathy of acquired immunodeficiency syndrome: preferential loss of the C-8 component of myelin basic protein.
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.
Wolf
D A
DA
Department of Pathology, University of Texas Medical Branch, Galveston 77550, USA.
Dholakia
S R
SR
Keherly
M J
MJ
Rodríguez-Wolf
M G
MG
Cloyd
M W
MW
Gelman
B B
BB
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000328:Adult; D015153:Blotting, Western; D003711:Demyelinating Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006868:Hydrolysis; D007150:Immunohistochemistry; D007536:Isomerism; D008297:Male; D008875:Middle Aged; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology
D004676:Myelin Basic Protein; D012333:RNA, Messenger