Apolipoprotein composition and particle size affect HDL degradation by chymase: effect on cellular cholesterol efflux
Mast cell chymase, a chymotrypsin-like neutral protease, can proteolyze HDL3. Here we studied the ability of rat and human chymase to proteolyze discoidal preβ-migrating reconstituted HDL particles (rHDLs) containing either apolipoprotein A-I (apoA-I) or apoA-II. Both chymases cleaved apoA-I in rHDL...
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| Format: | Article |
| Language: | English |
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Elsevier
2003-03-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520311937 |
| _version_ | 1818646770194841600 |
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| author | Miriam Lee Petri T. Kovanen Gabriella Tedeschi Emanuela Oungre Guido Franceschini Laura Calabresi |
| author_facet | Miriam Lee Petri T. Kovanen Gabriella Tedeschi Emanuela Oungre Guido Franceschini Laura Calabresi |
| author_sort | Miriam Lee |
| collection | DOAJ |
| description | Mast cell chymase, a chymotrypsin-like neutral protease, can proteolyze HDL3. Here we studied the ability of rat and human chymase to proteolyze discoidal preβ-migrating reconstituted HDL particles (rHDLs) containing either apolipoprotein A-I (apoA-I) or apoA-II. Both chymases cleaved apoA-I in rHDL at identical sites, either at the N-terminus (Tyr18 or Phe33) or at the C-terminus (Phe225), so generating three major truncated polypeptides that remained bound to the rHDL. The cleavage sites were independent of the size of the rHDL particles, but small particles were more susceptible to degradation than bigger ones. Chymase-induced truncation of apoA-I yielded functionally compromised rHDL with reduced ability to promote cellular cholesterol efflux. In sharp contrast to apoA-I, apoA-II was resistant to degradation. However, when apoA-II was present in rHDL that also contained apoA-I, it was degraded by chymase.We conclude that chymase reduces the ability of apoA-I in discoidal rHDL particles to induce cholesterol efflux by cleaving off either its amino- or carboxy-terminal portion. This observation supports the concept that limited extracellular proteolysis of apoA-I is one pathophysiologic mechanism leading to the generation and maintenance of foam cells in atherosclerotic lesions. |
| first_indexed | 2024-12-17T00:51:55Z |
| format | Article |
| id | doaj.art-1d1c1f58e42946248767ed4b882d5366 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T00:51:55Z |
| publishDate | 2003-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-1d1c1f58e42946248767ed4b882d53662022-12-21T22:09:43ZengElsevierJournal of Lipid Research0022-22752003-03-01443539546Apolipoprotein composition and particle size affect HDL degradation by chymase: effect on cellular cholesterol effluxMiriam Lee0Petri T. Kovanen1Gabriella Tedeschi2Emanuela Oungre3Guido Franceschini4Laura Calabresi5Wihuri Research Institute, Helsinki, Finland; Center E. Grossi Paoletti, Department of Pharmacological Sciences, University of Milan, Italy; Institute of Veterinary Physiology and Biochemistry, University of Milan, Italy; Faculty of Biology, University of Havana, CubaWihuri Research Institute, Helsinki, Finland; Center E. Grossi Paoletti, Department of Pharmacological Sciences, University of Milan, Italy; Institute of Veterinary Physiology and Biochemistry, University of Milan, Italy; Faculty of Biology, University of Havana, CubaWihuri Research Institute, Helsinki, Finland; Center E. Grossi Paoletti, Department of Pharmacological Sciences, University of Milan, Italy; Institute of Veterinary Physiology and Biochemistry, University of Milan, Italy; Faculty of Biology, University of Havana, CubaWihuri Research Institute, Helsinki, Finland; Center E. Grossi Paoletti, Department of Pharmacological Sciences, University of Milan, Italy; Institute of Veterinary Physiology and Biochemistry, University of Milan, Italy; Faculty of Biology, University of Havana, CubaWihuri Research Institute, Helsinki, Finland; Center E. Grossi Paoletti, Department of Pharmacological Sciences, University of Milan, Italy; Institute of Veterinary Physiology and Biochemistry, University of Milan, Italy; Faculty of Biology, University of Havana, CubaWihuri Research Institute, Helsinki, Finland; Center E. Grossi Paoletti, Department of Pharmacological Sciences, University of Milan, Italy; Institute of Veterinary Physiology and Biochemistry, University of Milan, Italy; Faculty of Biology, University of Havana, CubaMast cell chymase, a chymotrypsin-like neutral protease, can proteolyze HDL3. Here we studied the ability of rat and human chymase to proteolyze discoidal preβ-migrating reconstituted HDL particles (rHDLs) containing either apolipoprotein A-I (apoA-I) or apoA-II. Both chymases cleaved apoA-I in rHDL at identical sites, either at the N-terminus (Tyr18 or Phe33) or at the C-terminus (Phe225), so generating three major truncated polypeptides that remained bound to the rHDL. The cleavage sites were independent of the size of the rHDL particles, but small particles were more susceptible to degradation than bigger ones. Chymase-induced truncation of apoA-I yielded functionally compromised rHDL with reduced ability to promote cellular cholesterol efflux. In sharp contrast to apoA-I, apoA-II was resistant to degradation. However, when apoA-II was present in rHDL that also contained apoA-I, it was degraded by chymase.We conclude that chymase reduces the ability of apoA-I in discoidal rHDL particles to induce cholesterol efflux by cleaving off either its amino- or carboxy-terminal portion. This observation supports the concept that limited extracellular proteolysis of apoA-I is one pathophysiologic mechanism leading to the generation and maintenance of foam cells in atherosclerotic lesions.http://www.sciencedirect.com/science/article/pii/S0022227520311937apoA-I proteolysismast cell chymasereconstituted HDL |
| spellingShingle | Miriam Lee Petri T. Kovanen Gabriella Tedeschi Emanuela Oungre Guido Franceschini Laura Calabresi Apolipoprotein composition and particle size affect HDL degradation by chymase: effect on cellular cholesterol efflux Journal of Lipid Research apoA-I proteolysis mast cell chymase reconstituted HDL |
| title | Apolipoprotein composition and particle size affect HDL degradation by chymase: effect on cellular cholesterol efflux |
| title_full | Apolipoprotein composition and particle size affect HDL degradation by chymase: effect on cellular cholesterol efflux |
| title_fullStr | Apolipoprotein composition and particle size affect HDL degradation by chymase: effect on cellular cholesterol efflux |
| title_full_unstemmed | Apolipoprotein composition and particle size affect HDL degradation by chymase: effect on cellular cholesterol efflux |
| title_short | Apolipoprotein composition and particle size affect HDL degradation by chymase: effect on cellular cholesterol efflux |
| title_sort | apolipoprotein composition and particle size affect hdl degradation by chymase effect on cellular cholesterol efflux |
| topic | apoA-I proteolysis mast cell chymase reconstituted HDL |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520311937 |
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