Inhibition of Low density Lipoprotein Internalization and Transcytosis by HDL; an alternative role for “good” cholesterol

跨细胞 内化 清道夫受体 化学 脂蛋白 胆固醇 低密度脂蛋白 转染 内皮 细胞生物学 内科学 生物化学 受体 内吞作用 生物 医学 基因
作者
Karen Fung,Warren Lee,Greg Fairn
出处
期刊:The FASEB Journal [Wiley]
卷期号:34 (S1): 1-1 被引量:3
标识
DOI:10.1096/fasebj.2020.34.s1.00598
摘要

Atherosclerosis results from the build‐up of low‐density lipoprotein (LDL) cholesterol and immune cells in the arteries leading to their occlusion. High‐density lipoprotein (HDL) is believed to reverse this process by removing the arterial cholesterol from the body. Both LDL and HDL reach beneath the artery by crossing the endothelium through Scavenger receptor B1 (SR‐B1) mediated transcytosis. ApoAI, the protein exclusively found on HDL, mediates the interaction between HDL and SR‐B1. One natural ApoAI variant called Milano (ApoAI‐Mil) is of interest because injections of lipidated ApoAI‐Mil led to enhanced plaque regression. We hypothesize that the natural ability of ApoAI‐Mil to dimerize leads to better interaction with SR‐B1. This could result in better inhibition of LDL transcytosis since both HDL and LDL bind to SR‐B1 for transcytosis and this could also improve HDL transcytosis so that more HDL will reach the target tissue to extract cholesterol. We took an in vitro microscopy approach to quantify internalization of fluorescently labeled LDL in coronary endothelial cells. The ApoAI variants were also lipidated to form fluorescent HDL‐like particles (DiI‐DMPC‐WT or DiI‐DMPC‐Mil) to measure its association with SR‐B1 overexpressing cells. We observed that recombinant ApoAI‐WT can inhibit LDL internalization in coronary endothelial cells. There was also about an 8x‐fold increase of DiI‐DMPC‐WT fluorescence signal in HeLas overexpressing SR‐B1 compared to GFP alone. Furthermore, there was an even higher fold increase (~11x) of DiI‐DMPC‐Mil fluorescence signal compared to GFP alone. Similarly, excess recombinant ApoAI‐Mil led to greater inhibition of LDL internalization compared to ApoAI‐WT. There was no difference in the amount of DiI‐DMPC‐WT or ‐Mil associated with HeLa cells overexpressing Alk1, a LDL‐specific transcytosis receptor. Together this suggests that compared to ApoAI‐WT, ApoAI‐Mil more readily associates with only SR‐B1 which may lead to better inhibition of LDL internalization and to more HDL available to remove arterial cholesterol. Support or Funding Information Early Research Award & CIHR

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
咔咔完成签到 ,获得积分10
刚刚
1秒前
彭于晏应助暴躁的信封采纳,获得10
1秒前
害怕的宝川完成签到,获得积分20
1秒前
2秒前
华仔应助HUI采纳,获得10
4秒前
violet_项完成签到,获得积分10
4秒前
852应助辛勤的乌采纳,获得10
4秒前
5秒前
a7489420完成签到,获得积分20
5秒前
5秒前
songjin111111应助GY采纳,获得10
9秒前
9秒前
10秒前
10秒前
11秒前
十分喜欢完成签到 ,获得积分10
12秒前
xx发布了新的文献求助10
12秒前
13秒前
花园里的蒜完成签到 ,获得积分0
13秒前
11完成签到,获得积分10
15秒前
星辰坠于海应助zhong采纳,获得10
15秒前
忧郁的夏山关注了科研通微信公众号
15秒前
赘婿应助zhong采纳,获得10
15秒前
yuaner发布了新的文献求助10
16秒前
辛勤的乌发布了新的文献求助10
16秒前
qsy发布了新的文献求助10
16秒前
冬虫夏草发布了新的文献求助10
17秒前
大虎发布了新的文献求助10
18秒前
打打应助正直的发卡采纳,获得10
18秒前
SciGPT应助Skyler666采纳,获得50
18秒前
Singularity应助yuaner采纳,获得10
18秒前
今后应助科研通管家采纳,获得10
19秒前
Starwalker应助科研通管家采纳,获得20
19秒前
天天快乐应助科研通管家采纳,获得10
20秒前
传奇3应助科研通管家采纳,获得10
20秒前
Kevin应助科研通管家采纳,获得10
20秒前
20秒前
20秒前
高分求助中
좌파는 어떻게 좌파가 됐나:한국 급진노동운동의 형성과 궤적 2500
Sustainability in Tides Chemistry 1500
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
Cognitive linguistics critical concepts in linguistics 800
Threaded Harmony: A Sustainable Approach to Fashion 799
Livre et militantisme : La Cité éditeur 1958-1967 500
氟盐冷却高温堆非能动余热排出性能及安全分析研究 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3050909
求助须知:如何正确求助?哪些是违规求助? 2708236
关于积分的说明 7412010
捐赠科研通 2352411
什么是DOI,文献DOI怎么找? 1245174
科研通“疑难数据库(出版商)”最低求助积分说明 605463
版权声明 595796