Article(id=1291404919165154195, tenantId=1146029695717560320, journalId=1246415772164075586, issueId=1291404875351449891, articleNumber=null, orderNo=null, doi=10.13699/j.cnki.1001-6821.2025.09.005, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1733673600000, receivedDateStr=2024-12-09, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1785824525871, onlineDateStr=2026-08-04, pubDate=1747411200000, pubDateStr=2025-05-17, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1785824525871, onlineIssueDateStr=2026-08-04, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1785824525871, creator=13701087609, updateTime=1785824525871, updator=13701087609, issue=Issue{id=1291404875351449891, tenantId=1146029695717560320, journalId=1246415772164075586, year='2025', volume='41', issue='9', pageStart='1201', pageEnd='1350', issueExtLink='null', onlineDate='null', pubDate='1747411200000', pubDateStr='2025-05-17', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1785824515426, creator='13701087609', updateTime=1785824515426, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext=null, issueFiles=null, downloadFileDto=null}, startPage=1223, endPage=1228, ext={EN=ArticleExt(id=1291404919555224468, articleId=1291404919165154195, tenantId=1146029695717560320, journalId=1246415772164075586, language=EN, title=Inhibiting mitochondrial pyruvate carrier improved cuproptosis in SH-SY5Y cells treated with Okada, columnId=1246531407326105792, journalTitle=Chinese Journal of Clinical Pharmacology, columnName=Clinical and Basic Bridging Research, runingTitle=null, highlight=null, articleAbstract=
Objective To investigate the effect of inhibition of mitochondrial pyruvate carrier on Okada-induced cuprotosis in SH-SY5Y cells.
Methods SH-SY5Y cells were induced by okada acid (OA) to establish a model of Alzheimer’s disease (AD). The cells were divided into control group (complete medium), model group (20 nmol·L-1 OA) and experimental group [20 nmol·L-1 OA+1 μmol·L-1 2-cyano-3 -(1-phenyl-1H-indole-3-yl) -2-acrylic acid (UK-5099)]. Copper ion content was detected by cell cupric colorimetric kit. Pyruvate content was detect by pyruvate detection kit, and the expressions of phosphorylated Tau (AT8) and ferredoxin 1 (FDX1) in each group were detected by immunofluorescence staining. The expression levels of mitochondrial pyruvate carrier (MPC1/MPC2) and dihydrolipoyl transacetylase (DLAT) were detected by Western blot.
Results The contents of copper ions in experimental group, model group and control group were (0.36±0.01), (0.90±0.05) and (0.23±0.04) μmol·g prot-1; the pyruvate content were (0.55±0.04), (0.33±0.03) and (0.44±0.04) μmol·108 cell-1; the AT8 expression levels were 91.46±14.53, 125.02±14.43 and 72.57±19.81; the FDX1 expression levels were 98.93±7.40, 147.83±18.63 and 79.18±8.06; the relative expression levels of MPC1 protein were 0.59±0.11, 1.01±0.14 and 0.55±0.13; the relative expression levels of MPC2 protein were 0.54±0.05, 1.31±0.07 and 0.43±0.07; the relative expression levels of DLAT protein were 0.72±0.04, 0.92±0.07 and 0.53±0.14, respectively. The above indexes in the experimental group were statistically significant compared with those in the model group (P<0.05, P<0.01, P<0.001).
Conclusion Inhibition of mitochondrial pyruvate carrier can alleviate Okada-induced cuprotosis of SH-SY5Y cells.
, authors=Yue QI
1, Pei-chi HUANG
1, Wei CHEN
2, Xiao-bo DONG
2, Ji-tong LI
3, Zhao LI
4, authorsList=Yue QI, Pei-chi HUANG, Wei CHEN, Xiao-bo DONG, Ji-tong LI, Zhao LI, authorCompany=null, correspAuthors=Zhao LI, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1291404920322782101, articleId=1291404919165154195, tenantId=1146029695717560320, journalId=1246415772164075586, language=CN, title=抑制线粒体丙酮酸载体对冈田酸诱导SH-SY5Y神经元细胞铜死亡的作用机制, columnId=1246531407485489349, journalTitle=中国临床药理学杂志, columnName=临床与基础桥接研究, runingTitle=null, highlight=null, articleAbstract=
目的 研究抑制线粒体丙酮酸载体对冈田酸诱导SH-SY5Y神经元细胞铜死亡作用机制的影响。
方法 冈田酸（OA）诱导SH-SY5Y细胞建立阿尔茨海默病（AD）模型，将细胞分为对照组（完全培养基）、模型组（20 nmol·L-1 OA）和实验组[20 nmol·L-1 OA+1 μmol·L-1 2-氰基-3-（1-苯基-1H-吲哚-3-基）-2-丙烯酸（UK-5099）]。用细胞铜比色法测试盒检测铜离子含量，用丙酮酸检测试剂盒检测丙酮酸含量，用免疫荧光染色检测各组细胞内丝氨酸202/苏氨酸205位点磷酸化Tau（AT8）以及铁氧还蛋白1（FDX1）的表达情况，用蛋白质印迹法检测各组细胞内丙酮酸载体（MPC1/MPC2）和二氢硫辛酸转乙酰基酶（DLAT）的表达水平。
结果 实验组、模型组和对照组的铜离子含量分别为（0.36±0.01）、（0.90±0.05）和（0.23±0.04）μmol·g prot-1，丙酮酸含量分别为（0.55±0.04）、（0.33±0.03）和（0.44±0.04）μmol·108 cell-1，AT8表达水平分别为91.46±14.53、125.02±14.43和72.57±19.81，FDX1表达水平分别为98.93±7.40、147.83±18.63和79.18±8.06，MPC1蛋白相对表达水平分别为0.59±0.11、1.01±0.14和0.55±0.13，MPC2蛋白相对表达水平分别为0.54±0.05、1.31±0.07和0.43±0.07，DLAT蛋白相对表达水平分别为0.72±0.04、0.92±0.07和0.53±0.14，实验组的上述指标与模型组比较，在统计学上差异均有统计学意义（P<0.05，P<0.01，P<0.001）。
结论 抑制线粒体丙酮酸载体可以减轻冈田酸诱导的SH-SY5Y神经元细胞铜死亡。
, authors=齐越
1, 黄培池
1, 陈巍
2, 董笑博
2, 李纪彤
3, 李昭
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齐越（1977-），女，教授，主要从事中药新药药理及神经药理学的相关研究
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3.Department of General Practice, First Affiliated Hospitai of Ningbo University, Ningbo 315010, Zhejiang Province, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1291404922419934138, tenantId=1146029695717560320, journalId=1246415772164075586, articleId=1291404919165154195, authorId=1291404922285716407, language=CN, stringName=李纪彤, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=
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4.Department of Pharmacology, Shenyang Medical College, Shenyang 110002, Liaoning Province, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1291404922617066431, tenantId=1146029695717560320, journalId=1246415772164075586, articleId=1291404919165154195, authorId=1291404922487043004, language=CN, stringName=李昭, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=
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