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| Content Provider | Springer Nature Link |
|---|---|
| Author | Kumar, Bhupender Bamezai, Rameshwar N. K. |
| Copyright Year | 2015 |
| Abstract | Pyruvate kinase M2, an important metabolic enzyme, promotes aerobic glycolysis (Warburg effect) to facilitate cancer cell proliferation. Unravelling the status of this important glycolytic pathway enzyme under sub-lethal doses of etoposide, a commonly used anti-proliferative genotoxic drug to induce mild/moderate DNA damage in HeLa cells as a model system and discern its effect on: PKM2 expression, phosphorylation, dimer: tetramer ratio, activity and associated effects, was pertinent. Protein expression and phosphorylation of PKM2 from HeLa cells was estimated using Western blotting. Same protein lysate was also used to estimate total pyruvate kinase activity and the total dimer: tetramer content evaluated using glycerol gradient ultra-centrifugation. Intracellular PEP was estimated manually using standard curve; while NADPH was assessed by NADPH estimation kit. Unpaired t test and two-way-ANOVA was used for statistical analysis. A relative decrease in PKM2 expression and a subsequent dose and time dependent increase in Y105-phosphorylation were observed. A concomitant increase in PKM2 dimer content and Y105-phosphorylation responsible for reduced PKM2 activity promoted PEP accumulation and NADPH production, representing increased metabolic flux into PPP, a feature that favours cancer cells. It was apparent that the sub-lethal doses of etoposide induced inadequate damage to DNA in cancer cells in culture promoted pro-survival conditions due to Y105-phosphorylation of PKM2, its stable dimerization and inactivation, a unique association not known earlier, indicating what might happen in tumour revivals or recurrences. |
| Starting Page | 1317 |
| Ending Page | 1321 |
| Page Count | 5 |
| File Format | |
| ISSN | 03014851 |
| Journal | Molecular Biology Reports |
| Volume Number | 42 |
| Issue Number | 8 |
| e-ISSN | 15734978 |
| Language | English |
| Publisher | Springer Netherlands |
| Publisher Date | 2015-04-04 |
| Publisher Place | Dordrecht |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Etoposide DNA damage Pyruvate kinase M2 Glycolysis Pentose phosphate pathway Animal Biochemistry Animal Anatomy / Morphology / Histology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Medicine Molecular Biology |
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