Resveratrol prevents cadmium activation of Erk1/2 and JNK pathways from neuronal cell death via protein phosphatases 2A and 5.
Resveratrol prevents cadmium activation of Erk1/2 and JNK pathways from neuronal cell death via protein phosphatases 2A and 5.
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DOI：
10.1111/jnc.13233
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发表时间：
2015-11
影响因子：
4.7
通讯作者：
Chen, Long
中科院分区：
文献类型：
--
作者：
Liu, Chunxiao;Zhang, Ruijie;Sun, Chenxia;Zhang, Hai;Xu, Chong;Liu, Wen;Gao, Wei;Huang, Shile;Chen, Long
关键词：
镉(Cd)是一种有毒的环境污染物，可导致神经退行性疾病。白藜芦醇是一种天然产物，已被发现具有神经保护作用。然而，关于白藜芦醇对镉诱导的神经毒性的影响，人们知之甚少。在这里，我们发现白藜芦醇有效地逆转了镉诱导的神经细胞存活率下降、形态改变、核碎裂和凝聚以及caspase-3的激活，这意味着白藜芦醇对镉中毒具有神经保护作用。进一步研究发现，c-jun氨基末端激酶(JNK)和细胞外信号调节激酶1/2(ERK1/2)参与了白藜芦醇对Cd诱导的神经细胞死亡的抑制作用，白藜芦醇作为ERK1/2(U0126)和JNK(SP600125)的选择性抑制剂，或过表达显性负的丝裂原活化蛋白激酶1(MKK1)或显性负的c-Jun，增强了白藜芦醇对Cd诱导的神经细胞JNK和ERK1/2的磷酸化以及细胞死亡的抑制作用。有趣的是，白藜芦醇有效地将细胞从镉诱导的蛋白磷酸酶2A(PP2A)和5(PP5)活性的抑制中解救出来。PP2A或PP5的过表达增强了白藜芦醇对Cd诱导的ERK1/2和/或JNK的激活以及细胞死亡的抑制作用。结果表明，白藜芦醇可通过激活PP2A和PP5部分抑制Cd诱导的ERK1/2和JNK通路的激活和神经细胞死亡。我们的发现有力地支持了白藜芦醇可能作为潜在的治疗剂来预防镉诱导的神经退行性疾病的观点。
Cadmium (Cd), a toxic environmental contaminant, induces neurodegenerative disorders. Resveratrol, a natural product, has been found to exert neuroprotective effects. However, little is known regarding the effect of resveratrol on Cd-evoked neurotoxicity. Here, we show that resveratrol effectively reversed Cd-elicited cell viability reduction, morphological change, nuclear fragmentation and condensation, as well as activation of caspase-3 in neuronal cells, implying neuroprotection against Cd-poisoning by resveratrol. Further research revealed that both c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinases 1/2 (Erk1/2) were involved in the inhibitory effect of resveratrol on Cd-induced cell death, as selective inhibitors of Erk1/2 (U0126) and JNK (SP600125), or over-expression of dominant negative mitogen-activated protein kinase kinase 1 (MKK1) or dominant negative c-Jun potentiated resveratrol’s prevention of Cd-induced phosphorylation of JNK and Erk1/2, as well as cell death in neuronal cells. Interestingly, resveratrol potently rescued the cells from Cd-induced suppression of protein phosphatases 2A (PP2A) and 5 (PP5) activity. Over-expression of PP2A or PP5 strengthened the inhibitory effects of resveratrol on Cd-induced activation of Erk1/2 and/or JNK, as well as cell death. The results indicate that resveratrol prevents Cd-induced activation of Erk1/2 and JNK pathways and neuronal cell death in part via activating PP2A and PP5. Our findings strongly support the notion that resveratrol may serve as a potential therapeutic agent in the prevention of Cd-induced neurodegenerative diseases.
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影响因子：
7.4
作者：
Chen, Long;Xu, Baoshan;Liu, Lei;Luo, Van;Zhou, Hongyu;Chen, Wenxing;Shen, Tao;Han, Xiuzhen;Kontos, Christopher D.;Huang, Shile
通讯作者：
Huang, Shile
影响因子：
4.5
作者：
Eybl, Vladislav;Kotyzova, Dana;Koutensky, Jaroslav
通讯作者：
Koutensky, Jaroslav
影响因子：
5.7
作者：
Bai, Yu;Mao, Qi-Qi;Xie, Li-Ping
通讯作者：
Xie, Li-Ping
影响因子：
4.8
作者：
Huang, SL;Shu, LL;Houghton, PJ
通讯作者：
Houghton, PJ
Celastrol 通过靶向 JNK 和 PTEN-Akt/mTOR 网络来防止镉诱导的神经细胞死亡。
影响因子：
4.7
作者：
Chen S;Gu C;Xu C;Zhang J;Xu Y;Ren Q;Guo M;Huang S;Chen L
通讯作者：
Chen L