Stimulation of Gs and inhibition of Gi protein functions by minimally oxidized LDL.
Stimulation of Gs and inhibition of Gi protein functions by minimally oxidized LDL.
复制标题
最低限度氧化的 LDL 刺激 Gs 并抑制 Gi 蛋白功能。
DOI：
10.1161/01.atv.15.11.2019
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Berliner,JA
中科院分区：
文献类型：
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作者：
Parhami,F;Fang,ZT;Yang,B;Fogelman,AM;Berliner,JA
我们以前已经表明，用最低限度氧化的LDL（MM-LDL）处理主动脉内皮细胞会诱导它们与单核细胞而不是中性粒细胞的相互作用，并且这些诱导的反应与cAMP水平增加有关。在这里，我们研究了MM-LDL升高cAMP水平的机制。用MM-LDL处理人主动脉内皮细胞导致cAMP水平的饱和剂量依赖性增加。使用百日咳毒素和MM-LDL组合的研究表明，cAMP增加的部分原因是由于Gscomplex的刺激。使用百日咳毒素处理的膜进行研究，其中GI被完全抑制，以直接解决MM-LDL对Gspathway的影响。MM-LDL和氧化脂质（棕榈酰花生四烯酸磷脂酰胆碱），其作用类似于MM-LDL，引起这些分离的膜中cAMP水平增加40%至100%，GTP增强，从而显示GS刺激。这些结果还表明，MM-LDL通过抑制Gi增加cAMP水平。MM-LDL可抑制Giby的ADP核糖基化约30%，并完全消除5-羟色胺与Gicomplexes相互作用的能力，而Giby mastoparan的直接激活不受抑制。这一观察结果表明，MM-LDL干扰Gimolecules与抑制性受体的相互作用。MM-LDL对腺苷酸环化酶无直接影响。总体而言，这些研究表明，MM-LDL通过刺激G和抑制Gicomplex增加cAMP水平。
We have previously shown that treatment of aortic endothelial cells with minimally oxidized LDL (MM-LDL) induces their interaction with monocytes but not neutrophils and that these induced responses are associated with increased cAMP levels. Here we studied the mechanism by which MM-LDL elevates cAMP levels. Treatment of human aortic endothelial cells with MM-LDL resulted in a saturable dose-dependent increase in cAMP levels. Studies using a combination of pertussis toxin and MM-LDL suggested that part of the cAMP increase was due to the stimulation of Gscomplexes. Studies with pertussis toxin–treated membranes in which Giwas completely inhibited were used to directly address the effect of MM-LDL on the Gspathway. MM-LDL and an oxidized lipid (palmitoyl arachidonyl phosphatidylcholine), the effects of which mimic those of MM-LDL, caused a 40% to 100% increase in cAMP levels in these isolated membranes that was augmented by GTP, thus showing Gsstimulation. These results also show that MM-LDL increases cAMP levels by inhibiting Gi. MM-LDL inhibited ADP ribosylation of Giby about 30% and completely abolished the ability of serotonin to interact with Gicomplexes, whereas direct activation of Giby mastoparan was not inhibited. This observation suggests that MM-LDL interferes with the interaction of Gimolecules with inhibitory receptors. There was no direct effect of MM-LDL on adenylate cyclase. Overall, these studies show that MM-LDL increases cAMP levels both by stimulating Gsand inhibiting Gicomplexes.