烏頭堿誘導(dǎo)的心房顫動(dòng)對(duì)內(nèi)皮素1分泌及其受體表達(dá)的影響*

劉麗萍，趙鳳娟，張　博，洪　蘭，劉　霞，崔　勛(延邊大學(xué)醫(yī)學(xué)院生理學(xué)與病理生理學(xué)教研部，吉林延吉133002)

烏頭堿誘導(dǎo)的心房顫動(dòng)對(duì)內(nèi)皮素1分泌及其受體表達(dá)的影響*

劉麗萍，趙鳳娟，張博，洪蘭，劉霞，崔勛△
(延邊大學(xué)醫(yī)學(xué)院生理學(xué)與病理生理學(xué)教研部，吉林延吉133002)

目的:觀察和探討烏頭堿誘導(dǎo)的心房顫動(dòng)(房顫)對(duì)內(nèi)皮素1(ET-1)分泌及其受體表達(dá)的影響，并觀察ET-1下游的信號(hào)通路的變化。方法:采用大鼠左心房離體灌流模型，利用放射性免疫技術(shù)檢測(cè)ET-1分泌的水平;利用蛋白免疫印跡法分析心房肌縫隙連接蛋白40(Cx40)、43(Cx43)、ETA型受體(ETRA)、ETB型受體(ETRB)蛋白水平的變化以及MAPK/ERK和PI3K/ Akt的磷酸化作用。結(jié)果:房顫時(shí)Cx40和Cx43表達(dá)明顯下調(diào)(P＜0. 01) ;房顫明顯促進(jìn)心房ET-1的分泌(P＜0. 01) ;房顫時(shí)ET受體表達(dá)呈現(xiàn)異常，ETRA明顯上調(diào)(P＜0. 05)，而ETRB則顯著下調(diào)(P＜0. 01) ;房顫時(shí)ET-1下游的MAPK/ERK及PI3K/ Akt信號(hào)轉(zhuǎn)導(dǎo)發(fā)生變化，pERK及pAkt明顯上調(diào)(P＜0. 01，P＜0. 05)。結(jié)論:房顫明顯增加心房ET-1的分泌，并導(dǎo)致其受體及其下游ERK和Akt信號(hào)通路的異常表達(dá)，這可能與房顫誘導(dǎo)的心房肌結(jié)構(gòu)重構(gòu)相關(guān)。

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)

國(guó)家自然科學(xué)基金資助項(xiàng)目(No.81360061)

△E-mail: cuixun@ybu.edu.cn