Hydrogen sulfide inhibits MPP+-induced aldehyde stress and endoplasmic reticulum stress in PC12 cells: involving upregulation of BDNF
Hydrogen sulfide inhibits MPP+-induced aldehyde stress and endoplasmic reticulum stress in PC12 cells: involving upregulation of BDNF
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硫化氢抑制 PC12 细胞中 MPP 诱导的醛应激和内质网应激：涉及 BDNF 的上调
DOI：
10.1016/j.yexcr.2016.09.006
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发表时间：
2016
影响因子：
3.7
通讯作者：
Xiao-Qing Tang
中科院分区：
文献类型：
--
作者：
Fan Xiao;Ping Zhang;Ai-Hua Chen;Chun-Yan Wang;Wei Zou;Hong-Feng Gu;Xiao-Qing Tang
我们已经证实了硫化氢(H_2S)in1-Methy-4-Phe-nylpyridiniumIon(MPPþ)-induced神经毒性的保护作用，但这种保护的确切机制仍不清楚。丙醛应激和内质网应激在MPP神经毒性中起重要作用。脑源性神经营养因子(BDNF)是重要的内源性神经保护剂。因此，我们推测，H_2S对MPP？神经毒性的保护作用可能是通过上调BDNF来抑制MPP？诱导的乙醛应激和内质网应激。在本研究中，我们发现硫化钠能抑制MPP诱导的PC12细胞的醛应激(细胞内4-HNE和丙二醛的积累)和内质网应激(GRP78和裂解半胱氨酸酶-12的表达增加)，并上调暴露于MPP的PC12细胞的BDNFmRNA的表达。此外，我们还发现K252a和BDNF受体TrkB的抑制剂K252a预处理PC12细胞，notonlymarkedlyreversedtheinhibitioryroleofNaHSinMPPþ-induced醛脱氢酶应激，butalsoablatedtheprotectionofNaHSagainstMPPþ-induced神经毒性。这些数据证实了H_2S对MPP诱导的神经毒性的保护作用。
We hav epreviously demonstrated the protectiveaction of hydrogensulfide (H2S) in1-Methy-4-Phe-nylpyridiniumIon(MPPþ)-induced neurotoxicity.However,the exact mechanisms of this protection remain largelyunknown.Aldehyde stress and endoplasmic reticulum(ER) stress play significant roles in the neurotoxicityofMPPþ. Brain derived neurotrophic factor(BDNF) is an important endogenous neuro protectant. Therefore, we speculated that the protection of H2S against MPPþ neurotoxicity results from inhibiting MPPþ-induced aldehyde stress and ER stress via upregulation of BDNF. In the present.study, we found that NaHS, adonor of H2S, inhibited MPPþ-induced aldehyde stress (the accumulations of the intracellular 4-HNE and MDA)and ER stress(the increases in the expressions of GRP78 and Cleaved-caspase-12)in PC12 cells and upregulated the BDNFexpression in MPPþ-exposedPC12cells..Furthermore,wefoundthatpretreatmentofPC12cellswithK252a,aninhibitoroftheBDNFreceptorTrkB,notonlymarkedlyreversedtheinhibitioryroleofNaHSinMPPþ-induced aldehydestressandER stress, butalsoablatedtheprotectionofNaHSagainstMPPþ-induced neurotoxicity.These data de monstrated that the protective role of H2S against MPPþ-induced neurotoxicity by inhibitingaldehyde stress andERstress,whichisinvolvedinupregulationofBDNF.