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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Yin, Ke-jie Lee, Sungho Lopes, Kryslaine O. Zhang, Xulun Chen, Ying Sisodia, Sangram S. Cheng, Haipeng Li, Yue-ming Gong, Ping Vetrivel, Kulandaivelu S. Parent, Angèle T. Lee, Jin-moo Iwata, Nobuhisa Meckler, Xavier Thinakaran, Gopal Saido, Takaomi C. |
| Description | Author Affiliation: Vetrivel KS ( Department of Neurobiology and Neurology, The University of Chicago, Chicago, Illinois 60637, USA.) |
| Abstract | Cerebral deposition of beta-amyloid (Abeta) peptides is a pathological hallmark of Alzheimer disease. Intramembranous proteolysis of amyloid precursor protein by a multiprotein gamma-secretase complex generates Abeta. Previously, it was reported that CD147, a glycoprotein that stimulates production of matrix metalloproteinases (MMPs), is a subunit of gamma-secretase and that the levels of secreted Abeta inversely correlate with CD147 expression. Here, we show that the levels and localization of CD147 in fibroblasts, as well as postnatal expression and distribution in brain, are distinct from those of integral gamma-secretase subunits. Notably, we show that although depletion of CD147 increased extracellular Abeta levels in intact cells, membranes isolated from CD147-depleted cells failed to elevate Abeta production in an in vitro gamma-secretase assay. Consistent with an extracellular source that modulates Abeta metabolism, synthetic Abeta was degraded more rapidly in the conditioned medium of cells overexpressing CD147. Moreover, modulation of CD147 expression had no effect on epsilon-site cleavage of amyloid precursor protein and Notch1 receptor. Collectively, our results demonstrate that CD147 modulates Abeta levels not by regulating gamma-secretase activity, but by stimulating extracellular degradation of Abeta. In view of the known function of CD147 in MMP production, we postulate that CD147 expression influences Abeta levels by an indirect mechanism involving MMPs that can degrade extracellular Abeta. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 28 |
| Volume Number | 283 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2008-07-11 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Amyloid Beta-Protein Precursor Secretion Antigens, CD147 Metabolism Matrix Metalloproteinases Alzheimer Disease Genetics Pathology Amyloid Precursor Protein Secretases Animals Cell Line Cerebellum Gene Expression Regulation Mice Receptor, Notch1 Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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