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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 373 - 379 (7page)
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Background Nitric oxide synthases (NOSs) are a unique family of enzymes that catalyze the production of nitric oxide (NO) from l-arginine. Atherogenic action of oxidized low-density lipoproteins (oxLDL) may be mediated partly by the formation of NO in endothelial cells. Objective The objective of this study was to identify sources of reactive oxygen species (ROS) causing native LDL (nLDL)- induced senescence of cultured human umbilical vein endothelial cells (HUVECs). Methods HUVECs were treated with nLDL and NO production was assessed using Griess reagent as substrate and spectrophotometry in the absence or presence of specific inhibitors of endothelial NOS (eNOS) and inducible NOS (iNOS). In addition, expression levels of eNOS and iNOS were measured with ELISA and western blotting, and ROS was evaluated using 2′,7′-dichlorofluorescin diacetate (DCF-DA) and a fluorescence microplate reader. Results NO formation in nLDL-treated HUVECs was significantly increased. Long-term treatment with nLDL up-regulated both eNOS and iNOS proteins. Such increase of NO production in HUVECs induced by nLDL was significantly suppressed by treatment with iNOS-selective inhibitor 1400 W, but not by the eNOS-selective inhibitor L-NIO. Native LDL treatment uncoupled Hsp90, the regulatory binding protein of eNOS, from the enzyme in HUVECs. Native LDL also significantly increased ROS production in HUVECs. Conclusion These findings suggest that oxidative stress originated from induction of iNOS and eNOS could be a causative factor for nLDL-induced senescence of HUVECs.
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참고문헌 (40)
참고문헌 신청
Bredt DS / 1990 / Isolation of nitric oxide synthase, a calmodulin-requiring enzyme / Proc Natl Acad Sci USA 87:682~685
Bredt DS / 1991 / Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase / Nature 351:714~718
Dimmeler S / 1997 / Oxidized lowdensity lipoprotein induces apoptosis of human endothelial cells by activation of CPP32-like proteases. A mechanistic clue to the ‘response to injury’ hypothesis / Circulation 95(7):1760~1763
Ehara S / 2001 / Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes / Circulation 103:1955~1960
Galle J / 1995 / Impairment of endothelium-dependent dilation in rabbit renal arteries by oxidized lipoprotein(a). Role of oxygen-derived radicals / Circulation 92(6):1582~1589
Bredt DS / 1991 / Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase / Nature 351:714~718
Dimmeler S / 1997 / Oxidized lowdensity lipoprotein induces apoptosis of human endothelial cells by activation of CPP32-like proteases. A mechanistic clue to the ‘response to injury’ hypothesis / Circulation 95(7):1760~1763
Ehara S / 2001 / Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes / Circulation 103:1955~1960
Galle J / 1995 / Impairment of endothelium-dependent dilation in rabbit renal arteries by oxidized lipoprotein(a). Role of oxygen-derived radicals / Circulation 92(6):1582~1589
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