Inhibition of cPLA2 activation by Ginkgo biloba extract protects spinal cord neurons from glutamate excitotoxicity and oxidative stress-induced cell death.
Inhibition of cPLA2 activation by Ginkgo biloba extract protects spinal cord neurons from glutamate excitotoxicity and oxidative stress-induced cell death.
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DOI：
10.1111/j.1471-4159.2010.07160.x
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发表时间：
2011-03
影响因子：
4.7
通讯作者：
Xu XM
中科院分区：
文献类型：
--
作者：
Zhao Z;Liu N;Huang J;Lu PH;Xu XM
银杏叶提取物（EGb 761）已被证明是神经保护;然而，EGb 761介导神经保护的机制仍不清楚。我们假设EGb 761的神经保护作用是通过抑制胞浆磷脂酶A2（cPLA 2）介导的，cPLA 2是一种已知在急性脊髓损伤（SCI）后介导继发性发病机制中起关键作用的酶。为了确定EGb 761神经保护是否涉及cPLA 2通路，我们首先研究了谷氨酸和过氧化氢（H2 O2）对cPLA 2活化的影响。结果显示，两种损伤均诱导磷酸化cPLA 2（p-cPLA 2）（cPLA 2活化的标志物）表达增加，并诱导体外神经元死亡。EGb 761给药可显著逆转上述效应。此外，EGb 761显著降低前列腺素E2（PGE 2）的释放，前列腺素E2是cPLA 2的下游代谢产物。此外，用花生四烯酸三氟甲基酮（ATK）抑制cPLA 2活性可改善对谷氨酸和H2 O2诱导的神经元死亡的神经保护作用，并逆转Bcl-2/Bax比值;值得注意的是，EGb 761产生的作用大于ATK。最后，我们发现ERK 1/2信号通路参与EGb 761对cPLA 2磷酸化的调节。这些结果共同表明，EGb 761的保护作用是介导的，至少部分是通过抑制cPLA 2激活，ERK 1/2信号通路可能在介导EGb 761的作用中发挥重要作用。
Ginkgo biloba extract (EGb761) has been shown to be neuroprotective; however, the mechanism by which EGb761 mediates neuroprotection remains unclear. We hypothesized that the neuroprotective effect of EGb761 is mediated by inhibition of cytosolic phospholipase A2 (cPLA2), an enzyme that is known to play a key role in mediating secondary pathogenesis after acute spinal cord injury (SCI). To determine whether EGb761 neuroprotection involves the cPLA2 pathway, we first investigated the effect of glutamate and hydrogen peroxide (H2O2) on cPLA2 activation. Results showed that both insults induced an increase in the expression of phosphorylated cPLA2 (p-cPLA2), a marker of cPLA2 activation, and neuronal death in vitro. Such effects were significantly reversed by EGb761 administration. Additionally, EGb761 significantly decreased prostaglandin E2 (PGE2) release, a downstream metabolite of cPLA2. Moreover, inhibition of cPLA2 activity with arachidonyl trifluromethyl ketone (ATK) improved neuroprotection against glutamate and H2O2-induced neuronal death, and reversed Bcl-2/Bax ratio; notably, EGb761 produced greater effects than ATK. Finally, we showed that the ERK1/2 signaling pathway is involved in EGb761’s modulation of cPLA2 phosphorylation. These results collectively suggest that the protective effect of EGb761 is mediated, at least in part, through inhibition of cPLA2 activation, and that the ERK1/2 signaling pathway may play an important role in mediating the EGb761’s effect.
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影响因子：
15.9
作者：
GRONICH, J;KONIECZKOWSKI, M;SEDOR, JR
通讯作者：
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作者：
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