D-Glucose upregulates adenosine transport in cultured human aortic smooth muscle cells.
D-Glucose upregulates adenosine transport in cultured human aortic smooth muscle cells.
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D-葡萄糖上调培养的人主动脉平滑肌细胞中的腺苷转运。
DOI：
10.1152/ajpheart.00921.2004
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Tse,Chung-Ming
中科院分区：
文献类型：
--
作者：
Leung,GeorgePH;Man,RickyYK;Tse,Chung-Ming
糖尿病患者发生动脉粥样硬化的病因尚不清楚。腺苷已被证明能抑制大鼠主动脉平滑肌细胞的生长。核苷转运蛋白通过调节腺苷受体附近的腺苷水平在腺苷功能中发挥不可或缺的作用。因此，我们研究了模拟糖尿病高血糖的25 mM葡萄糖对培养的人主动脉平滑肌细胞（HASMCs）腺苷转运的影响。尽管RT-PCR证实了平衡型核苷转运蛋白-1（ENT-1）和ENT-2 mRNA的存在，但功能研究表明，HASMCs中腺苷转运主要由ENT-1介导，并被硝基苄基巯基嘌呤核苷（NBMPR，IC 50 = 0.69 ± 0.05 nM）抑制。用25 mM葡萄糖处理48 h后，HASMCs的腺苷转运增加>30%，但用甘露醇和葡萄糖处理则没有增加。动力学研究表明，d-葡萄糖增加腺苷转运的Vmax，而不影响Km。同样地，d-葡萄糖增加了高亲和力[3 H]NBMPR结合的Bmax，而解离常数（Kd）没有改变。与这些观察结果一致，25 mM-葡萄糖增加ENT-1的mRNA和蛋白质表达。用MAPK/ERK的选择性抑制剂PD-98059（40 μM）和U-0126（10 μM）处理血清饥饿的细胞，消除了d-葡萄糖对ENT-1的作用。我们得出的结论是，d-葡萄糖上调HASMC中ENT-1的蛋白质和信息表达以及功能活性，可能是通过MAPK/ERK依赖性途径实现的。在病理学上，糖尿病中ENT-1活性的增加可能影响腺苷受体附近腺苷的可用性，从而改变糖尿病中的血管功能。
The etiology of the atherosclerosis that occurs in diabetes mellitus is unclear. Adenosine has been shown to inhibit growth of rat aortic smooth muscle cells. Nucleoside transporters play an integral role in adenosine function by regulating adenosine levels in the vicinity of adenosine receptors. Therefore, we studied the effect of 25 mMd-glucose, which mimics hyperglycemia of diabetes, on adenosine transport in cultured human aortic smooth muscle cells (HASMCs). Although RT-PCR demonstrated the presence of equilibrative nucleoside transporter-1 (ENT-1) and ENT-2 mRNA, functional studies revealed that adenosine transport in HASMCs was predominantly mediated by ENT-1 and inhibited by nitrobenzylmercaptopurine riboside (NBMPR, IC50= 0.69 ± 0.05 nM). Adenosine transport in HASMCs was increased by >30% after treatment for 48 h with 25 mMd-glucose, but not with equimolard-mannitol andl-glucose. Kinetic studies showed thatd-glucose increasedVmaxof adenosine transport without affectingKm. Similarly,d-glucose increased Bmaxof high-affinity [3H]NBMPR binding, while the dissociation constant (Kd) was not changed. Consistent with these observations, 25 mMd-glucose increased mRNA and protein expression of ENT-1. Treatment of serum-starved cells with the selective inhibitors of MAPK/ERK, PD-98059 (40 μM) and U-0126 (10 μM), abolished the effect ofd-glucose on ENT-1. We conclude thatd-glucose upregulates the protein and message expression and functional activity of ENT-1 in HASMCs, possibly via MAPK/ERK-dependent pathways. Pathologically, the increase in ENT-1 activity in diabetes may affect the availability of adenosine in the vicinity of adenosine receptors and, thus, alter vascular functions in diabetes.
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DOI：
10.1152/ajprenal.1997.273.6.f1058
发表时间：
1997-12-01
影响因子：
4.2
作者：
Wang, J;Su, SF;Giacomini, KM
通讯作者：
Giacomini, KM
影响因子：
8.3
作者：
Dubey, RK;Gillespie, DG;Jackson, EK
通讯作者：
Jackson, EK
DOI：
10.1152/ajpcell.1997.272.2.c707
发表时间：
1997-02
期刊：
The American journal of physiology
影响因子：
--
作者：
M. Ritzel;S. Yao;M.-Y. Huang;J. Elliott;C. Cass;J. Young
通讯作者：
M. Ritzel;S. Yao;M.-Y. Huang;J. Elliott;C. Cass;J. Young
培养的动脉平滑肌细胞中腺苷受体介导的环 AMP 产生和 DNA 合成的变化
影响因子：
5.6
作者：
B. Jonzon;B. Fredholm;J. Nilsson
通讯作者：
J. Nilsson
早期给予 YT-146（一种腺苷 A2 受体激动剂）可抑制大鼠股动脉内皮损伤后的新生内膜增厚。
影响因子：
5
作者：
Y. Takiguchi;Mitsuyo Nagano;Y. Ikeda;M. Nakashima
通讯作者：
M. Nakashima