Purification and characterization of brain clusterin.
Clusterin, a 70-80 kDa sulfated glycoprotein found in numerous tissues, is also known as complement lysis inhibitor (CLI), apolipoprotein J, SP-40,40, TRPM-2, and SGP-2. In Alzheimer disease (AD), clusterin mRNA is increased, whereas clusterin protein is found in deposits of beta-amyloid (A beta). These studies characterized clusterin protein from human brain. In extracts from cortex and hippocampus, clusterin was about 40% higher in AD than in controls. Purified clusterin from human brain was slightly smaller than serum clusterin. Brain and serum clusterin were indistinguishable in the inhibition of complement-mediated hemolysis. Both serum and brain clusterin were indistinguishable in inhibiting the aggregation of A beta and promoting oxidative stress in rat pheochromocytoma PC12 cells (MTT assay). The inhibition of A beta aggregation and enhancement of A beta toxicity by clusterin suggest new mechanisms in AD.
Oda
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T
Andrus Gerontology Center, University of Southern California, Los Angeles 90089-0191.
Pasinetti
G M
GM
Osterburg
H H
HH
Anderson
C
C
Johnson
S A
SA
Finch
C E
CE
D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D051152:Clusterin; D003169:Complement Inactivator Proteins / Q000302:isolation & purification* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression; D006023:Glycoproteins / Q000096:biosynthesis / Q000302:isolation & purification* / Q000494:pharmacology*; D006168:Guinea Pigs; D006461:Hemolysis / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D006825:Hybridomas; D015151:Immunoblotting; D018832:Molecular Chaperones; D008970:Molecular Weight; D012333:RNA, Messenger / Q000096:biosynthesis; D012016:Reference Values
D000911:Antibodies, Monoclonal; C495242:CLU protein, human; D051152:Clusterin; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D018832:Molecular Chaperones; D012333:RNA, Messenger