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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2018.1
- 수록면
- 366 - 375 (10page)
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초록· 키워드
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Purpose: Vascular smooth muscle cell (VSMC) proliferation induced by native low-density lipoprotein (nLDL) stimulation is dependenton superoxide production from activated NADPH oxidase. The present study aimed to investigate whether the novel arginaseinhibitor limonin could suppress nLDL-induced VSMC proliferation and to examine related mechanisms. Materials and Methods: Isolated VSMCs from rat aortas were treated with nLDL, and cell proliferation was measured by WST-1and BrdU assays. NADPH oxidase activation was evaluated by lucigenin-induced chemiluminescence, and phosphorylation ofprotein kinase C (PKC) βII and extracellular signal-regulated kinase (ERK) 1/2 was determined by western blot analysis. Mitochondrialreactive oxygen species (ROS) generation was assessed using MitoSOX-red, and intracellular L-arginine concentrationswere determined by high-performance liquid chromatography (HPLC) in the presence or absence of limonin. Results: Limonin inhibited arginase I and II activity in the uncompetitive mode, and prevented nLDL-induced VSMC proliferationin a p21Waf1/Cip1-dependent manner without affecting arginase protein levels. Limonin blocked PKCβII phosphorylation,but not ERK1/2 phosphorylation, and translocation of p47phox to the membrane was decreased, as was superoxide productionin nLDL-stimulated VSMCs. Moreover, mitochondrial ROS generation was increased by nLDL stimulation and blocked by preincubationwith limonin. Mitochondrial ROS production was responsible for the phosphorylation of PKCβII. HPLC analysisshowed that arginase inhibition with limonin increases intracellular L-arginine concentrations, but decreases polyamine concentrations. L-Arginine treatment prevented PKCβII phosphorylation without affecting ERK1/2 phosphorylation. Conclusion: Increased L-arginine levels following limonin-dependent arginase inhibition prohibited NADPH oxidase activationin a PKCβII-dependent manner, and blocked nLDL-stimulated VSMC proliferation.
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참고문헌 (38)
참고문헌 신청
Locher R / 2002 / Native LDL induces proliferation of human vascular smooth muscle cells via redoxmediated activation of ERK 1/2 mitogen-activated protein kinases / Hypertension 39(2):645~650
Sachinidis A / 1990 / Novel cellular activities for low density lipoprotein in vascular smooth muscle cells / Hypertension 15(6):704~711
박일환 / 2015 / NADPH oxidase activation contributes to native low-density lipoprotein-induced proliferation of human aortic smooth muscle cells / Experimental and Molecular Medicine 47:1~10
Chidambara Murthy KN / 2011 / Citrus limonin and its glucoside inhibit colon adenocarcinoma cell proliferation through apoptosis / J Agric Food Chem 59:2314~2323
Vanamala J / 2006 / Suppression of colon carcinogenesis by bioactive compounds in grapefruit / Carcinogenesis 27:1257~1265
Sachinidis A / 1990 / Novel cellular activities for low density lipoprotein in vascular smooth muscle cells / Hypertension 15(6):704~711
박일환 / 2015 / NADPH oxidase activation contributes to native low-density lipoprotein-induced proliferation of human aortic smooth muscle cells / Experimental and Molecular Medicine 47:1~10
Chidambara Murthy KN / 2011 / Citrus limonin and its glucoside inhibit colon adenocarcinoma cell proliferation through apoptosis / J Agric Food Chem 59:2314~2323
Vanamala J / 2006 / Suppression of colon carcinogenesis by bioactive compounds in grapefruit / Carcinogenesis 27:1257~1265
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