Prostaglandin E2 negatively regulates AMP-activated protein kinase via protein kinase A signaling pathway
Prostaglandin E2 negatively regulates AMP-activated protein kinase via protein kinase A signaling pathway
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DOI：
10.1016/j.prostaglandins.2008.09.002
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发表时间：
2009-01-01
影响因子：
2.9
通讯作者：
Kambe, Fukushi
中科院分区：
文献类型：
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作者：
Funahashi, Koji;Cao, Xia;Kambe, Fukushi
我们研究了前列腺素（PG）E2可能参与AMP激活蛋白激酶（AMPK）的调节。当成骨细胞MG 63在无血清培养基中培养时，AMIN α-submit的Thr-172磷酸化显著增加。用PGE 2处理细胞显著降低了磷酸化。丝氨酸-79磷酸化的乙酰辅酶A羧化酶，AMPK的直接目标，也减少了PG E2。另一方面，PC E2可增加α-亚基的Ser-485磷酸化，这可能与AMPK活性的抑制有关。PGE 2的这些作用被PGE 2受体EP 2和EP 4激动剂和毛喉素模拟，但不被EP 1和EP 3激动剂模拟，并且该作用被腺苷酸环化酶抑制剂SQ 22536和蛋白激酶A抑制剂H89抑制。此外，PGE 2的作用在原代颅骨成骨细胞中重复。总之，本研究表明，PGE 2通过激活蛋白激酶A信号通路负调节AMPK活性。(C)2008年爱思唯尔公司All rights reserved.
We investigated possible involvement of prostaglandin (PG) E2 in regulation of AMP-activated protein kinase (AMPK). When osteoblastic MG63 cells were Cultured in serum-deprived media, Thr-172 phosphorylation of AMIN alpha-submit was markedly increased. Treatment of the cells with PGE2 significantly reduced the phosphorylation. Ser-79 phosphorylation of acetyl-CoA carboxylase, a direct target for AMPK, was also reduced by PG E2. On the other hand, PC E2 reciprocally increased Ser-485 phosphorylation of the a-subunit that could be associated with inhibition of AMPK activity. These effects of PGE2 were mimicked by PGE2 receptor EP2 and EP4 agonists and forskolin, but not by EP1 and EP3 agonists, and the effects were suppressed by an adenylate cyclase inhibitor SQ22536 and a protein kinase A inhibitor H89. Additionally, the PGE2 effects were duplicated in primary calvarial osteoblasts. Together, the present Study demonstrates that PGE2 negatively regulates AMPK activity via activation of protein kinase A signaling pathway. (C) 2008 Elsevier Inc. All rights reserved.