혈관내피세포에서 카바밀화 알부민이 산소결핍 유도 인자-1에 미치는 영향

Other Titles
Effects of Carbamylated Albumin on Hypoxia Inducible Factor-1 in Human Umbilical Vein Endothelial Cells
Authors
김민수
Issue Date
2013-12
Awarded Date
2014
Abstract
Carbamylated albumin may reduce the endothelial dysfunction via inactivation HIF-1 and decrease in reactive oxygen species (ROS) production, leading to inhibition of the progression of atherosclerosis. To test this hypothesis, the levels of calcium, endothelial nitric oxide synthase (eNOS), ROS and HIF-1 in the human umbilical vein endothelial cells were measured. Ten to 1,000 μg/mL albumin was carbamylated as described by Horkko et al. ROS level was measured with 2´,7´‐dichlorofluorescin diacetate using VICTOR3TM multilabelcounter. The level of calcium ion in the hypoxic state was higher than that in the control state. ROS production was decreased depending on the concentration of the carbamylated abumin. And ROS level after treatment of carbamylated albumin in HUVECs was lower that after treatment of non-carbamylated albumin in HUVECs. The ROS levels in the groups with carbamylated albumin treatment were lower than those in the controls. The levels of calcium, p-eNOS, HIF-1 and p-Akt in the hypoxic state was higher than those in the control state. The levels of calcium, p-eNOS, HIF-1 and p-Akt in the hypoxic group with carbamylated albumin treatment to HUVECs were lower than those without carbamylated albumin treatment to the HUVECs. According to these results, carbamylated albumin reduces endothelial dysfunction via inhibition of HIF-1 and attenuation of ROS including NO production, thus leading to delay in the progression of atherosclerosis
카바밀화된 알부민은 산소결핍 유도인자-1(HIF-1)과 활성산소의 감소를 유도하여 혈관내피 세포의 기능장애를 감소시켜 동맥경화증의 진행을 감소시킬 수 있을지 여부를 확인하기 위하여 인체 태반정맥에서 얻은 혈관 내피세포에서 칼슘, 내피세포의 산화질소 합성효소(eNOS), 활성산소 및 HIF-1을 측정하였다. 10에서 1,000 μg/mL 알부민을 Horkko 등의 방법으로 카바밀화 시켰으며, 활성산소치는 시약으로 2´,7´‐dichlorofluorescin diacetate를 사용하여 VICTOR3TM multilabelcounter로 측정하였다. 산소결핍시에 칼슘 이온의 농도는 대조군에 비해 높았다. 활성산소 생성량은 카바밀화된 알부민의 농도에 비례하여 감소되었다. 또한 인체 태반정맥에서 카바밀화된 알부민을 처리하였을 때 활성산소치는 대조군에 비해 낮았으며, 카바밀화되지 않은 알부민을 처리하였을 때에 비해서도 낮았다. 산소결핍시에는 칼슘, 인산화된 eNOS, HIF-1과 인산화된-Akt치가 모두 대조군에 비해 높았으며, 카바밀화된 알부민을 처리하였을 때는 카바밀화되지 않은 알부민을 처리하였을 때에 비해서 이들 수치들이 모두 낮았다. 이러한 결과로 보아, 혈관내피세포에서 카바밀화된 알부민은 HIF-1을 억제하고, 산화질소를 비롯한 활성산소 생성을 억제하여 혈관내피 세포의 기능장애를 감소시켜 동맥경화증의 진행을 감소시키는 것으로 생각된다.
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/11458
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3. Thesis (학위논문) > 1. School of Medicine (의과대학) > 석사
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http://dcollection.kmu.ac.kr//jsp/common/DcLoOrgPer.jsp?sItemId=000000020924
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