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GRP78 protects CHO cells from ribosylation
Wu, Beibei1; Yu, Lexiang1,5; Hu, Pingdong1,5; Lu, Yang1; Li, Juan2; Wei, Yan1; He, Rongqiao1,2,3,4; Y. Wei; R. He
2018-04-01
发表期刊BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
通讯作者邮箱yanwei@ibp.ac.cn ; rongqiaohe@163.com
ISSN0167-4889
文章类型Article
卷号1865期号:4页码:629-637
产权排序1,2
摘要

D-Ribose (Rib), a reactive glycation compound that exists in organisms, abnormally increases in the urine of diabetic patients and can yield large amounts of advanced glycation end products (AGEs), leading to cell dysfunction. However, whether cellular proteins are sensitive to this type of glycation is unknown. In this study, we found that cellular AGEs accumulate in Chinese hamster ovary (CHO) cells with increased Rib concentration and administration time. Mass spectrum analysis of isolated AGE-modified proteins from cell lysates showed that glucose-regulated protein 78 kD (GRP78) is one of the main ribosylated proteins. Co-immunoprecipitation assays further confirmed the interaction between AGEs and GRP78. Compared with D-glucose (Glc), Rib produced much more AGEs in cells. In kinetic studies, the first order rate constant of LDH released from CHO cells incubated with Rib was nearly 8-fold higher than that of Glc, suggesting that Rib is highly cytotoxic. Immunofluorescent co-localization analysis manifested partial superimposition of AGEs and GRP78, which were distributed throughout the endoplasmic reticulum. Western blotting showed that the expression of GRP78 is up-regulated and then down-regulated in CHO cells during Rib treatment. In the presence of Rib, the suppression of GRP78 expression either with transfected siRNA or with the inhibitor (-)-epigallocatechin gallate (EGCG) dramatically increased AGE levels and decreased cell viability compared with these parameters in the control groups. GRP78 over-expression decreased AGE levels and rescued the cells from Rib-induced cytotoxicity. These data indicate that GRP78 plays a role in preventing Rib-induced CHO cell cytotoxicity.

关键词D-Ribose GRP78 Glycation AGEs Cytotoxicity
DOI10.1016/j.bbamcr.2018.02.001
收录类别SCI
语种英语
项目资助者Natural Scientific Foundation of China NSFC(31270868 ; National Key Research and Development Program of China(2016YFC1305900) ; Beijing Municipal Science and Technology Project(Z161100000217141 ; QCAS Biotechnology Fund(GJHZ1131) ; Youth Innovation Promotion Association CAS(2017132) ; 31670805) ; Z161100000216137)
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
WOS类目Biochemistry & Molecular Biology ; Cell Biology
WOS记录号WOS:000427335700009
WOS标题词Science & Technology ; Life Sciences & Biomedicine
关键词[WOS]GLYCATION END-PRODUCTS ; ENDOPLASMIC-RETICULUM STRESS ; GLUCOSE-REGULATED PROTEIN ; ER STRESS ; D-RIBOSE ; CEREBROSPINAL-FLUID ; ACTIVATION ; APOPTOSIS ; INDUCTION ; ACCUMULATION
引用统计
文献类型期刊论文
条目标识符http://ir.psych.ac.cn/handle/311026/26049
专题脑与认知科学国家重点实验室
通讯作者Y. Wei; R. He
作者单位1.Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, 15 Datun Rd, Beijing 100101, Peoples R China
2.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing 100101, Peoples R China
3.Southwest Med Univ, Luzhou 646000, Sichuan, Peoples R China
4.Capital Med Univ, Beijing Inst Brain Disorders, Alzheimers Dis Ctr, Beijing 10069, Peoples R China
5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714
Wu, Beibei,Yu, Lexiang,Hu, Pingdong,et al. GRP78 protects CHO cells from ribosylation[J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH,2018,1865(4):629-637.
APA Wu, Beibei.,Yu, Lexiang.,Hu, Pingdong.,Lu, Yang.,Li, Juan.,...&R. He.(2018).GRP78 protects CHO cells from ribosylation.BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH,1865(4),629-637.
MLA Wu, Beibei,et al."GRP78 protects CHO cells from ribosylation".BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH 1865.4(2018):629-637.
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