Oxidative stress contributes to the pathogenesis of neurodegenerative diseases.With the aim to find reagents that reduce oxidative stress,a phage display library was screened for peptides mimicking a2,6-sialyllactose(...Oxidative stress contributes to the pathogenesis of neurodegenerative diseases.With the aim to find reagents that reduce oxidative stress,a phage display library was screened for peptides mimicking a2,6-sialyllactose(6'-SL),which is known to beneficially influence neural functions.Using Sambucus nigra lectin,which specifically binds to 6'-SL,we screened a phage display library and found a peptide comprising identical sequences of 12 amino acids.Mimetic peptide,reverse peptide and scrambled peptide were tested for inhibition of 6'-SL binding to the lectin.Indeed,lectin binding to 6'-SL was inhibited by the most frequently identified mimetic peptide,but not by the reverse or scrambled peptides,showing that this peptide mimics 6'-SL.Functionally,mimetic peptide,but not the reverse or scrambled peptides,increased viability and expression of neural cell adhesion molecule L1 in SK-N-SH human neuroblastoma cells,and promoted survival and neurite outgrowth of cultured mouse cerebellar granule neurons challenged by H_20_2-induced oxidative stress.The combined results indicate that the 6'-SL mimetic peptide promotes neuronal survival and neuritogenesis,thus raising hopes for the treatment of neurodegenerative diseases.This study was approved by the Medical Ethics Committee of Shantou University Medical College,China(approval No.SUMC 2014-004)on February 20,2014.展开更多
基金supported by the National Natural Science Foundation of China,No.81471279 and No.81171138(to WJZ)Talent Support Grant from Shantou University Medical College,China,No.2501220118(to WJZ)the Li Kashing Foundation,No.LD030302(to MS)
文摘Oxidative stress contributes to the pathogenesis of neurodegenerative diseases.With the aim to find reagents that reduce oxidative stress,a phage display library was screened for peptides mimicking a2,6-sialyllactose(6'-SL),which is known to beneficially influence neural functions.Using Sambucus nigra lectin,which specifically binds to 6'-SL,we screened a phage display library and found a peptide comprising identical sequences of 12 amino acids.Mimetic peptide,reverse peptide and scrambled peptide were tested for inhibition of 6'-SL binding to the lectin.Indeed,lectin binding to 6'-SL was inhibited by the most frequently identified mimetic peptide,but not by the reverse or scrambled peptides,showing that this peptide mimics 6'-SL.Functionally,mimetic peptide,but not the reverse or scrambled peptides,increased viability and expression of neural cell adhesion molecule L1 in SK-N-SH human neuroblastoma cells,and promoted survival and neurite outgrowth of cultured mouse cerebellar granule neurons challenged by H_20_2-induced oxidative stress.The combined results indicate that the 6'-SL mimetic peptide promotes neuronal survival and neuritogenesis,thus raising hopes for the treatment of neurodegenerative diseases.This study was approved by the Medical Ethics Committee of Shantou University Medical College,China(approval No.SUMC 2014-004)on February 20,2014.
文摘目的检测子痫前期孕妇血清中人端粒酶反转录酶(human telomerase reverse transcriptase,hTERT)、沉默信息调节因子6(silent information regulator 6,Sirt6)表达,并探究hTERT,Sirt6水平表达与疾病严重程度及妊娠结局评估中的价值。方法选取2018年1月~2022年12月在陕西省人民医院进行诊治的300例子痫前期孕妇作为子痫前期组,孕妇均符合《妊娠期高血压疾病诊治指南(2015)》中子痫前期诊断标准,选取同时期孕检的300例健康孕妇为对照组,根据病情严重程度将子痫前期组分为轻症子痫前期组(n=180)和重症子痫前期组(n=120),根据是否发生不良妊娠结局将子痫前期组分为正常妊娠组(n=165)和不良妊娠组(n=135)。酶联免疫吸附实验(enzyme-linked immunosorbnent assay,ELISA)法检测血清中hTERT和Sirt6水平,Spearman相关性分析血清中hTERT和Sirt6水平与子痫前期孕妇病情严重程度的相关性,利用受试者工作特征(receiver operating characteristic,ROC)曲线评估血清hTERT和Sirt6水平在子痫前期诊断及妊娠结局预测中的价值。结果与对照组比较,子痫前期组血清hTERT(22.15±5.82 ng/ml vs 30.12±9.56 ng/ml),Sirt6(5.26±1.62 ng/ml vs 7.06±2.29 ng/ml)水平降低,差异具有统计学意义(t=12.334,11.114,均P<0.001)。与轻症子痫前期组比较,重症子痫前期组孕妇血清hTERT(18.28±4.11 ng/ml vs 24.73±6.96 ng/ml),Sirt6(4.03±1.17 ng/ml vs 6.08±1.92 ng/ml)水平降低,差异具有统计学意义(t=9.142,10.469,均P<0.001)。与正常妊娠组比较,不良妊娠组子痫前期孕妇血清中hTERT(17.75±4.61 ng/ml vs 25.75±6.81 ng/ml),Sirt6(4.06±0.96 ng/ml vs 6.24±2.16 ng/ml)水平降低,差异具有统计学意义(t=11.639,10.878,均P<0.001)。Spearman相关性分析显示,血清hTERT,Sirt6水平与子痫前期孕妇疾病严重程度均呈负相关(r=-0.562,-0.604,均P<0.001)。ROC曲线分析结果显示,血清hTERT,Sirt6诊断子痫前期的曲线下面积(95%置信区间)[AUC(95%CI)]分别为0.711(0.673~0.747),0.727(0.689~0.762),两者联合诊断子痫前期的AUC(95%CI)为0.788(0.753~0.820),高于两者单独诊断(Z=2.719,2.154,P=0.007,0.031);血清hTERT,Sirt6预测子痫前期不良妊娠结局的AUC(95%CI)分别为0.786(0.735~0.831),0.783(0.732~0.829),两者联合预测子痫前期不良妊娠结局的AUC(95%CI)为0.849(0.804~0.888),高于两者单独预测(Z=1.855,1.861,P=0.032,0.031)。结论hTERT和Sirt6在子痫前期孕妇血清中水平较低,与子痫前期孕妇疾病严重程度均呈负相关,并对妊娠结局具有一定的评估价值。