Inhibition of chymase activity by phosphoglycerides |
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| Affiliation: | 1. Department of Thoracic and Vascular Surgery, Arnaud de Villeneuve Hospital, Montpellier, France;2. INSERM U 1046, Montpellier, France;1. Division of Pediatric and Congenital Cardiothoracic Surgery, Arkansas Children’s Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas;2. Biostatistics Program, Department of Pediatrics, Arkansas Children’s Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas;3. Center for Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, Little Rock, Arkansas;4. Children’s Medical Center, Department of Pediatric Cardiovascular Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan;1. Department of Pathology, Federal University of Santa Catarina, Florianópolis, SC, Brazil;2. Dental School, Federal University of Santa Catarina, Florianopolis, SC, Brazil;3. University Hospital, Federal University of Santa Catarina, Florianopolis, SC, Brazil;1. Sol Price School of Public Policy, University of Southern California, 650 Childs Way, Los Angeles, CA 90089, United States;2. Schwarzenegger Institute for State and Global Policy, University of Southern California, 635 Downey Way, VPD 201, Los Angeles, CA 90089-3331, United States;1. Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina;2. Section of Molecular Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina;3. Department of Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina;4. Hypertension and Vascular Research Center, Wake Forest School of Medicine, Winston-Salem, North Carolina;5. Department of Physiology & Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina;6. Department of Cardiothoracic Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina |
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| Abstract: | The activity of chymase was markedly inhibited by phosphoglycerides such as phosphatidic acid, phosphatidylserine, and phosphatidylinositol, but was not affected by acylglycerides, phosphoglyceroserine, serine, inositol, or glycerol. These results suggest that both the nonpolar hydrophobic hydrocarbon tails and the polar hydrophilic head are essential for the inhibitory effects of phosphoglycerides. Binding of a primary amine to an anionic polar head of phosphatidic acid, such as in phosphatidylserine and phosphatidylethanolamine, slightly decreased the inhibitory effect of phosphatidic acid and, conversely, binding of a strong cation to the head, such as in phosphatidylcholine, resulted in its activation of chymase. Phosphatidic acid containing an unsaturated fatty acid, such as dioleoyl phosphatidic acid, caused the same extent of inhibition as natural phosphatidic acid from bovine brain, but was 20 times more inhibitory than phosphatidic acid containing a saturated fatty acid, such as distearoyl phosphatidic acid. The inhibition by phosphatidylserine was noncompetitive and pseudoirreversible, and the Ki value was 0.54 μm. The inhibition of chymase by phosphatidylserine was pH dependent, being strong at pH 8.5 to 9.5 but weak below pH 7.5. Phosphatidylserine specifically inhibited chymase and elastase; it did not inhibit the other chymotrypsin-type serine endopeptidases tested, trypsin, papain, collagenase, carboxypeptidase A, or cathepsin D. |
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