Hesperetin induces glyoxalase 1 enhancement in SH-SY5Y cells cultured with high glucose via Nrf2/ARE activation  

作　　者：ZHANG Meng-ya LIU Yao-wu 

机构地区：[1]Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy,Xuzhou Medical University,Xuzhou 221004,China [2]Department of Pharmacy,Zhengzhou Central Hospital Affiliated to Zhengzhou University,Zhengzhou 450007,China [3]Department of Pharmacology,School of Pharmacy,Xuzhou Medical University,Xuzhou 221004,China

出　　处：《中国药理学与毒理学杂志》2019年第9期702-702,共1页Chinese Journal of Pharmacology and Toxicology

基　　金：National Natural Science Foundation of China(81371210)

摘　　要：OBJECTIVE To investigate the neuroprotective effects of hesperetin on central neurons under chronic high glucose,and the relationship to glyoxalase 1(Glo-1),a cytoprotective enzyme.METHODS The human neuroblas⁃toma SH-SY5Y cells were divided into 5 groups:normal glucose,high glucose(HG),HG plus low,middle,or high concentra⁃tion of hesperetin(1,5,25μmol·L^-1).After treatment for 72 h,neuron damages,Glo-1 expressions and functions,as well as Nrf2/ARE pathway and its regulating mechanisms were examined.RESULTS Hesperetin increased cell viability and decreased lactate dehydrogenase release,which was accompanied by the elevated activity,protein,and mRNA levels of Glo-1 as well as the enhanced Glo-1 functions in SH-SY5Y cells cultured with HG.Moreover,hesperetin activated Nrf2/ARE pathway as evidenced by the raised Nrf2 and p-Nrf2 levels in nucleus and up-regulation of γ-glutamycysteine synthase(γ-GCS),a well-known target gene of Nrf2/ARE pathway.Nevertheless,pretreatment with a PKC inhibitor(Go 6983)or an Akt inhibitor(MK-22062HCl,reflecting GSK-3β activation)abolished the effect of hesperetin on protein expressions of Glo-1 and γ-GCS.CONCLUSION Hesperetin exerted the neuroprotection by promoting Glo-1 function in central neurons in long-term HG condition,which was mediated by activation of Nrf2/ARE pathway;moreover,the increased Nrf2 phosphorylation and nuclear translocation mediated by PKC activation and/or GSK-3β inhibition were involved in the activation of Nrf2/ARE pathway by hesperetin.OBJECTIVE To investigate the neuroprotective effects of hesperetin on central neurons under chronic high glucose, and the relationship to glyoxalase 1（Glo-1）, a cytoprotective enzyme. METHODS The human neuroblastoma SH-SY5 Y cells were divided into 5 groups: normal glucose, high glucose（HG）, HG plus low, middle, or high concentration of hesperetin(1, 5, 25 μmol·L-1). After treatment for 72 h, neuron damages, Glo-1 expressions and functions, as well as Nrf2/ARE pathway and its regulating mechanisms were examined. RESULTS Hesperetin increased cell viability and decreased lactate dehydrogenase release, which was accompanied by the elevated activity, protein, and mRNA levels of Glo-1 as well as the enhanced Glo-1 functions in SH-SY5 Y cells cultured with HG. Moreover, hesperetin activated Nrf2/ARE pathway as evidenced by the raised Nrf2 and p-Nrf2 levels in nucleus and up-regulation of γ-glutamycysteine synthase（γ-GCS）, a well-known target gene of Nrf2/ARE pathway. Nevertheless, pretreatment with a PKC inhibitor（Go6983） or an Akt inhibitor（MK-2206 2 HCl, reflecting GSK-3β activation） abolished the effect of hesperetin on protein expressions of Glo-1 and γ-GCS. CONCLUSION Hesperetin exerted the neuroprotection by promoting Glo-1 function in central neurons in long-term HG condition, which was mediated by activation of Nrf2/ARE pathway; moreover, the increased Nrf2 phosphorylation and nuclear translocation mediated by PKC activation and/or GSK-3β inhibition were involved in the activation of Nrf2/ARE pathway by hesperetin.

关 键 词：HESPERETIN NEUROPROTECTION glyoxalase 1 Nrf2/ARE pathway GSK-3Β 

分 类 号：R73[医药卫生—肿瘤]