Hwang Yong Pil, Jeong Hye Gwang
Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University, 375 Seosuk-dong, Gwangju, Republic of Korea.
FEBS Lett. 2008 Jul 23;582(17):2655-62. doi: 10.1016/j.febslet.2008.06.045. Epub 2008 Jun 30.
In this study, we investigated the mechanisms of kahweol protection of neuronal cells from cell death induced by the Parkinson's disease-related neurotoxin 6-hydroxydopamine (6-OHDA). Pretreatment of SH-SY5Y cells with kahweol significantly reduced 6-OHDA-induced generation of ROS, caspase-3 activation, and subsequent cell death. Kahweol also up-regulated heme oxygenase-1 (HO-1) expression, which conferred neuroprotection against 6-OHDA-induced oxidative injury. Moreover, kahweol induced PI3K and p38 activation, which are involved in the induction of Nrf2, HO-1 expression, and neuroprotection. These results suggest that regulation of the anti-oxidant enzyme HO-1 via the PI3K and p38/Nrf2 signaling pathways controls the intracellular levels of ROS.
在本研究中，我们探究了卡维醇保护神经元细胞免受帕金森病相关神经毒素6-羟基多巴胺（6-OHDA）诱导的细胞死亡的机制。用卡维醇预处理SH-SY5Y细胞可显著减少6-OHDA诱导的活性氧生成、半胱天冬酶-3激活及随后的细胞死亡。卡维醇还上调了血红素加氧酶-1（HO-1）的表达，从而赋予对6-OHDA诱导的氧化损伤的神经保护作用。此外，卡维醇诱导了PI3K和p38的激活，这与Nrf2的诱导、HO-1的表达及神经保护有关。这些结果表明，通过PI3K和p38/Nrf2信号通路对抗氧化酶HO-1的调节控制了细胞内活性氧的水平。
