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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Zhang, Guanglin Sun, Li Lu, Xianghong Chen, Zhanghui Duerksen-Hughes, Penelope J. Hu, Hu Zhu, Xinqiang Yang, Jun |
| Description | Country affiliation: China Author Affiliation: Zhang G ( The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China.) |
| Abstract | Using a proteomic approach, we have previously shown that exposure to different concentrations of cisplatin during a 12-h period can lead to changes in nuclear protein expression and alternative splicing in HeLa cells. To further shed light on the DNA damage response (DDR) induced by cisplatin, we examined the nuclear proteome profiles of HeLa cells treated with 5µM cisplatin for different times (2, 12, and 24h). Two-dimensional electrophoresis (2-DE) identified 98 differentially expressed proteins in cisplatin-treated cells as compared to control cells. Among them, 54 spots (55%) were down-regulated and 44 spots (45%) were up-regulated. 51 spots were subjected to Matrix-assisted-laser-desorption-ionization Time-of-flight/time-of-flight Mass spectrometry (MALDI-TOF/TOF MS) identification, and 40 spots were identified. Among these, 22 proteins were located in nucleus. These proteins were involved in stress response, cell cycle and division, apoptosis, mRNA processing, transport, splicing and microRNA (miRNA) maturation. The changed expression of Annexin A1 and Lamin B1 were confirmed by Western blot. The role of Annexin A1 in the response to cisplatin-induced DNA damage was further analyzed, and it was shown that after Annexin A1 knockdown, cisplatin-induced DNA damage was significantly increased. In addition, the changed expression of several miRNAs was also observed by quantitative real-time PCR (qRT-PCR). Taken together, these data indicate that cisplatin-induced DDR is a complex process, and that those proteins identified by proteomics can lead to new directions for a better understanding of this process. |
| File Format | HTM / HTML |
| ISSN | 13835718 |
| e-ISSN | 18793592 |
| Journal | Mutation Research/Genetic Toxicology and Environmental Mutagenesis |
| Issue Number | 1 |
| Volume Number | 746 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2012-07-04 |
| Publisher Place | Netherlands |
| Access Restriction | Open |
| Subject Keyword | Micrornas Research Support, Non-u.s. Gov't Discipline Genetics Toxicity Cell Survival Discipline Biochemistry Antineoplastic Agents Metabolism Drug Effects Cisplatin Dna Damage Nuclear Proteins Gene Knockdown Techniques Transfection Annexin A1 Dose-response Relationship, Drug Genetics Hela Cells |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Health, Toxicology and Mutagenesis |
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