OSU53 Rescues Human OB-6 Osteoblastic Cells from Dexamethasone through Activating AMPK Signaling.
OSU53 Rescues Human OB-6 Osteoblastic Cells from Dexamethasone through Activating AMPK Signaling.
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OSU53 通过激活 AMPK 信号从地塞米松中拯救人类 OB-6 成骨细胞
DOI：
10.1371/journal.pone.0162694
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Cui ZM
中科院分区：
文献类型：
--
作者：
Xu D;Zhao W;Zhu X;Fan J;Cui S;Sun Y;Chen X;Liu W;Cui ZM
地塞米松(Dex)的过量应用会导致成骨细胞死亡，从而导致骨质疏松或骨坏死。AMP活化蛋白激酶(AMPK)的激活被证明可以保护成骨细胞/成骨细胞免受地塞米松的伤害。在这篇报道中，我们测试了一种新的AMPK激活剂OSU53在地塞米松处理的成骨细胞中的潜在作用。我们发现OSU53激活了人OB-6成骨细胞中的AMPK信号。此外，地塞米松诱导的成骨细胞OB-6细胞死亡和凋亡在很大程度上被OSU53预先处理而减弱。OSU53比其他已知的AMPK激动剂(A-769662和化合物13)更有效地保护OB-6细胞对抗地塞米松。OSU53对OB-6细胞的作用需要AMPK的激活。AMPKαshRNA敲除或显性负突变(dN-AMPKαT172a)几乎完全阻断OSU53诱导的AMPK激活和OB-6细胞对地塞米松的保护作用。进一步的研究表明，OSU53提高了OB-6细胞的NADPH(烟酰胺腺嘌呤二核苷酸磷酸)活性，并减轻了地塞米松诱导的氧化应激。在OB-6细胞中，OSU53的这种作用又被AMPKαshRNA或dN-AMPKα几乎消除。综上所述，这些结果表明OSU53可能通过激活AMPK依赖的信号来保护成骨细胞免受地塞米松的伤害。
Excessive dexamethasone (Dex) application causes osteoblast cell death, which could lead to osteoporosis or osteonecrosis. AMP-activated protein kinase (AMPK) activation is shown to protect osteoblasts/osteoblastic cells from Dex. In this report, we tested the potential effect of OSU53, a novel AMPK activator, in Dex-treated osteoblastic cells. We show that OSU53 activated AMPK signaling in human OB-6 osteoblastic cells. Further, Dex-induced osteoblastic OB-6 cell death and apoptosis were largely attenuated with pre-treatment with OSU53. OSU53 was more efficient than other known AMPK activators (A-769662 and Compound 13) in protecting OB-6 cells against Dex. AMPK activation is required for OSU53-induced actions in OB-6 cells. AMPKα shRNA knockdown or dominant-negative mutation (dn-AMPKα T172A) almost completely blocked OSU53-induced AMPK activation and OB-6 cell protection against Dex. Further studies showed that OSU53 increased NADPH (nicotinamide adenine dinucleotide phosphate) activity and alleviated Dex-induced oxidative stress in OB-6 cells. Such effects by OSU53 were again almost abolished with AMPKα shRNA or dn-AMPKα in OB-6 cells. Together, these results demonstrate that OSU53 protects osteoblastic cells from Dex possibly via activating AMPK-dependent signaling.
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影响因子：
7.3
作者：
Guh JH;Chang WL;Yang J;Lee SL;Wei S;Wang D;Kulp SK;Chen CS
通讯作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1016/j.jsbmb.2009.02.007
发表时间：
2009-04
期刊：
The Journal of steroid biochemistry and molecular biology
影响因子：
--
作者：
Kerachian MA;Séguin C;Harvey EJ
通讯作者：
Harvey EJ