乌头碱诱导的心房颤动对内皮素1分泌及其受体表达的影响*

刘丽萍，赵凤娟，张　博，洪　兰，刘　霞，崔　勋(延边大学医学院生理学与病理生理学教研部，吉林延吉133002)

乌头碱诱导的心房颤动对内皮素1分泌及其受体表达的影响*

刘丽萍，赵凤娟，张博，洪兰，刘霞，崔勋△
(延边大学医学院生理学与病理生理学教研部，吉林延吉133002)

目的:观察和探讨乌头碱诱导的心房颤动(房颤)对内皮素1(ET-1)分泌及其受体表达的影响，并观察ET-1下游的信号通路的变化。方法:采用大鼠左心房离体灌流模型，利用放射性免疫技术检测ET-1分泌的水平;利用蛋白免疫印迹法分析心房肌缝隙连接蛋白40(Cx40)、43(Cx43)、ETA型受体(ETRA)、ETB型受体(ETRB)蛋白水平的变化以及MAPK/ERK和PI3K/ Akt的磷酸化作用。结果:房颤时Cx40和Cx43表达明显下调(P＜0. 01) ;房颤明显促进心房ET-1的分泌(P＜0. 01) ;房颤时ET受体表达呈现异常，ETRA明显上调(P＜0. 05)，而ETRB则显著下调(P＜0. 01) ;房颤时ET-1下游的MAPK/ERK及PI3K/ Akt信号转导发生变化，pERK及pAkt明显上调(P＜0. 01，P＜0. 05)。结论:房颤明显增加心房ET-1的分泌，并导致其受体及其下游ERK和Akt信号通路的异常表达，这可能与房颤诱导的心房肌结构重构相关。

AIM: To unravel the metabolic phenotype of human hematopoietic progenitor and stem cells (HPSCs).METHODS: Flow cytometric profiling and separation of human MPB cells based on their mitochondrial activity were performed using MitoTracker dyes and used for further analysis of metabolic profiles and underlying mechanisms.RESULTS: We showed that HPSCs had a similar metabolic phenotype，as shown by high rates of glycolysis and low rates oxygen consumption.Fractionation of human mobilized peripheral blood cells based on their metabolic footprint showed that the cells with a low mitochondrial potential were highly enriched for HPSCs.Remarkably，low MP cells had much better repopulation ability as compared to high MP cells.Moreover，similar to their murine counterparts，Hif-1α was upregulated in human HPSCs，where it was transcriptionally regulated by Meis1.Finally，Meis1 and its cofactors Pbx1 and HoxA9 played an important role in transcriptional activation of Hif-1α in a cooperative manner.CONCLUSION: These findings highlight the unique metabolic properties of human HPSCs and the transcriptional network that regulates their metabolic phenotype.

△Corresponding author E-mail: zhengjunke@shsmu.edu.cn

▲These authors contribute equally to this work

Hypoxic metabolism in human hematopoietic stem cells

Fatih KOCABAS1▲，XIE Li2▲，Hesham A.SADEK1，ZHANG Cheng-cheng1，ZHENG Jun-ke2△
(1Department of Internal Medicine，Division of Cardiology，UT Southwestern Medical Center at Dallas，Dallas，TX 75390，USA;
2Key Laboratory of Cell Differentiation and Apoptosis，Chinese Ministry of Education，Shanghai Jiaotong University School of Medicine，Shanghai 200025，China)

国家自然科学基金资助项目(No.81360061)

△E-mail: cuixun@ybu.edu.cn