Activation of members of the mitogen-activated protein kinase family by glucose in endothelial cells
Activation of members of the mitogen-activated protein kinase family by glucose in endothelial cells
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DOI：
10.1152/ajpendo.2000.279.4.e782
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发表时间：
2000-10-01
影响因子：
5.1
通讯作者：
Lowe, WL
中科院分区：
文献类型：
--
作者：
Liu, WL;Schoenkerman, A;Lowe, WL
为了更好地了解高血糖诱导内皮细胞粥样硬化改变的分子机制，我们在牛肺动脉内皮细胞（PAEC）中检测了高糖对丝裂原活化蛋白激酶（MAPK）家族成员，包括c-Jun nh2末端激酶（JNK）、细胞外信号调节激酶(ERK)- 1、-2和-5以及p38激酶的激活的影响。葡萄糖、果糖和棉子糖诱导PAEC生长的浓度依赖性下降。在正常生长培养基中加入25 mM葡萄糖、果糖或棉子糖可刺激JNK1活性增加约两倍，并在24小时后达到最大值，而只有葡萄糖可显著增加ERK5活性。葡萄糖、果糖或棉子糖均未增加ERK1/2和p38激酶活性。抗氧化剂n -乙酰半胱氨酸部分消除了葡萄糖诱导的ERK5活性的增加，但对JNK1活性的增加没有影响。相比之下，azaserine可以阻止己糖胺途径的通量增加，降低葡萄糖诱导的JNK1活性，但对果糖或棉子糖诱导的JNK1活性没有影响。与这一发现一致，葡萄糖胺刺激JNK1活性增加2.4倍，重现了葡萄糖对PAEC生长的抑制作用。总之，葡萄糖通过不同的机制激活PAEC中MAPK家族的不同成员。此外，不同糖激活JNK1和抑制细胞生长能力之间的相关性表明，该信号通路的激活可能有助于葡萄糖在内皮细胞中的生长抑制作用。
To better understand the molecular mechanisms for hyperglycemia-induced proatherogenic changes in endothelial cells, the effect of high glucose on activation of members of the mitogen-activated protein kinase (MAPK) family, including c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK)- 1, -2, and -5, and p38 kinase, was examined in bovine pulmonary artery endothelial cells (PAEC). Glucose, fructose, and raffinose induced a concentration-dependent decrease in PAEC growth. Addition of 25 mM glucose, fructose, or raffinose to normal growth medium stimulated an approximately twofold increase in JNK1 activity that was maximal after 24 h, whereas only glucose markedly increased ERK5 activity. Neither ERK1/2 nor p38 kinase activity was increased by glucose, fructose, or raffinose. The antioxidant N-acetylcysteine partially abrogated the glucose-induced increase in ERK5 activity but had no effect on the increase in JNK1 activity. In contrast, azaserine, which prevents increased flux through the hexosamine pathway, decreased glucose-induced JNK1 activity but had no effect on fructose- or raffinose-induced JNK1 activity. Consistent with this finding, glucosamine stimulated a 2.4-fold increase in JNK1 activity and reproduced the inhibitory effect of glucose on PAEC growth. In summary, glucose activates different members of the MAPK family in PAEC via distinct mechanisms. Moreover, the correlation between the ability of different sugars to activate JNK1 and inhibit cell growth suggests that activation of this signaling pathway may contribute to the growth inhibitory effect of glucose in endothelial cells.