4-Methylcatechol-induced heme oxygenase-1 exerts a protective effect against oxidative stress in cultured neural stem/progenitor cells via PI3 kinase/Akt pathway
4-Methylcatechol-induced heme oxygenase-1 exerts a protective effect against oxidative stress in cultured neural stem/progenitor cells via PI3 kinase/Akt pathway
复制标题
DOI：
10.2220/biomedres.31.45
复制
发表时间：
2010-02-01
影响因子：
1.2
通讯作者：
Furukawa, Shoei
中科院分区：
文献类型：
--
作者：
Furukawa, Yoshiko;Urano, Tomomi;Furukawa, Shoei
4-甲基儿茶酚(4MC)是多种细胞合成神经营养素家族成员的刺激物，它能上调神经干/祖细胞(NS/PC)中氧化还原敏感的诱导型应激蛋白-血红素氧合酶(HO)-1的表达。RT-PCR分析显示，4MC以剂量和时间依赖的方式诱导HO-1mRNA表达。ELISA法和Western blotting分析证实，HO-1mRNA的增加伴随着HO-1蛋白含量的增加。当NS/PCs在过氧化氢(H_2O_2)暴露前用4MC预处理时，大部分细胞从H_2O_2诱导的死亡中解救出来。4MC以时间依赖的方式促进丝裂原活化蛋白激酶(MAPK)/细胞外信号调节蛋白激酶(ERK)和Akt的磷酸化。PI3K/Akt信号转导通路在4MC诱导的HO-1表达和神经保护作用中起重要作用。综上所述，我们的结果表明，4MC通过PI3K/Akt信号通路激活HO-1的表达，HO-1蛋白抑制氧化应激诱导的NS/PC的死亡。
4-Methylcatechol (4MC), a stimulator of the synthesis of neurotrophin family members in various cells, was able to up-regulate the expression of heme oxygenase (HO)-1, a redox-sensitive inducible stress protein, in neural stem/progenitor cells (NS/PCs). RT-PCR analysis showed that 4MC induced HO-1 mRNA expression in a dose- and a time-dependent manner. The increase in HO-1 mRNA was followed by an increase in HO-1 protein content, which was confirmed by ELISA and Western blotting analysis. When NS/PCs,were pretreated with 4MC before exposure to hydrogen peroxide (H2O2), most of the cells were rescued from the H2O2-induced death. 4MC enhanced the phosphorylation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) and Akt in a time-dependent manner. Pretreatment Of Cultures with a selective inhibitor of PI3 kinase (PI3K)/Akt, but not with one of MAPK/ERK, inhibited both the 4MC-induced HO-1 expression and neuroprotective effect, demonstrating that PI3K/Akt signaling pathway played a significant role in 4MC-induced HO-1 induction and neuroprotection. Taken together, Our results suggest that 4MC activates the expression of HO-1 through the PI3K/Akt signaling pathway and that the HO-1 protein inhibits the death of NS/PCs induced by oxidative stress.