Human serum paraoxonases (PON1) Q and R selectively decrease lipid peroxides in human coronary and carotid atherosclerotic lesions - PON1 esterase and peroxidase-like activities
Human serum paraoxonases (PON1) Q and R selectively decrease lipid peroxides in human coronary and carotid atherosclerotic lesions - PON1 esterase and peroxidase-like activities
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DOI：
10.1161/01.cir.101.21.2510
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发表时间：
2000-05-30
期刊：
影响因子：
37.8
通讯作者：
Rosenblat, M
中科院分区：
文献类型：
--
作者：
Aviram, M;Hardak, E;Rosenblat, M
背景-人血清对氧磷酶（PON 1）以两种多态形式存在：第一种在位置192处的氨基酸（谷氨酰胺和精氨酸，分别为Q和R）不同，第二种在位置55处的氨基酸（甲硫氨酸和亮氨酸，分别为M和L）不同。PON 1保护LDL氧化，并在LDL氧化过程中，PON 1是inactivated.Methods和Results-The本研究比较PON 1亚型Q和R对人冠状动脉和颈动脉病变的脂质过氧化物含量的影响。与PON 1 Q或PON 1 R（10芳基酯酶单位/mL）孵育24小时后，冠状动脉和颈动脉病变匀浆（0.1 g/mL）中的脂质过氧化物含量分别降低至27%和16%。上述孵育分别使PON 1 Q和PON 1 R失活15%和45%。损伤部位的亚油酸胆固醇酯过氧化氢和氢氧化亚油酸胆固醇酯被PON 1水解，产生亚油酸过氧化氢和氢氧化亚油酸。此外，损伤和纯的亚油酸氢过氧化物被还原产生亚油酸氢氧化物，这些结果表明PON 1表现出酯酶样和过氧化物酶样活性。重组PON 1突变体，其中PON 1-自由巯基在半胱氨酸-284被替换为丙氨酸或丝氨酸不再能够减少过氧化脂质含量在颈动脉lesions. Conclusions，我们的结论是，PON 1可能是抗动脉粥样硬化，因为它水解过氧化脂质在人类动脉粥样硬化病变。
Background-Human serum paraoxonase (PON1) exists in two polymorphic forms: one that differs in the amino acid at position 192 (glutamine and arginine, Q and R, respectively) and the second one that differs in the amino acid at position 55 (methionine and leucine, M and L, respectively). PON1 protects LDL from oxidation, and during LDL oxidation, PON1 is inactivated.Methods and Results-The present study compared PON1 isoforms Q and R for their effect on lipid peroxide content in human coronary and carotid lesions. After 24 hours of incubation with PON1Q or PON1R (10 arylesterase units/mL), lipid peroxides content in both coronary and carotid lesion homogenates (0.1 g/mL) was reduced up to 27% and 16%, respectively. The above incubation was associated with inactivation of PON1Q and PON1R by 15% and 45%, respectively. Lesion cholesteryl linoleate hydroperoxides and cholesteryl linoleate hydroxides were hydrolyzed by PON1 to yield linoleic acid hydroperoxides and linoleic acid hydroxides. Furthermore, lesion and pure linoleic acid hydroperoxides were reduced to yield linoleic acid hydroxides, These results thus indicate that PON1 demonstrates esterase-like and peroxidase-like activities. Recombinant PON1 mutants in which the PON1-free sulfhydryl group at cysteine-284 was replaced with either alanine or serine were no longer able to reduce lipid peroxide content in carotid lesions.Conclusions-We conclude that PON1 may be antiatherogenic because it hydrolyzes lipid peroxides in human atherosclerotic lesions.