Increased expression and phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoforms in urinary exosomes in pre-eclampsia
Abstract Background Glycolysis is altered in various kidney diseases, but little is known about glycolysis in pre-eclampsia, a multi-system disorder with major pathological effects on the kidney. Urinary exosomes provide a non-invasive alternative for studying changes in kidney metabolism. This stud...
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| Format: | Article |
| Language: | English |
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BMC
2019-02-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12967-019-1806-6 |
| _version_ | 1819158975953764352 |
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| author | R. Ellis M. Katerelos S. W. Choy N. Cook M. Lee K. Paizis G. Pell S. Walker D. A. Power P. F. Mount |
| author_facet | R. Ellis M. Katerelos S. W. Choy N. Cook M. Lee K. Paizis G. Pell S. Walker D. A. Power P. F. Mount |
| author_sort | R. Ellis |
| collection | DOAJ |
| description | Abstract Background Glycolysis is altered in various kidney diseases, but little is known about glycolysis in pre-eclampsia, a multi-system disorder with major pathological effects on the kidney. Urinary exosomes provide a non-invasive alternative for studying changes in kidney metabolism. This study aims to characterise the expression and phosphorylation of isozymes of the key glycolytic regulatory protein, 6-phosphofructokinase-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2), in urinary exosomes of subjects with pre-eclampsia (PE), compared to normotensive non-pregnant (NC) and normotensive pregnant (NP) controls. Methods A cross-sectional study of NC (n = 19), NP (n = 23) and PE (n = 29) subjects was performed. Exosomes were isolated from urine samples by differential ultracentrifugation, and then analyzed by Western blot and densitometry for expression of PFK-2/FBPase-2 isozymes (PFKFB2, PFKFB3 and PFKFB4) and phosphorylation of PFKFB2 at residues Ser483 and Ser466 and PFKFB3 at Ser461. Results PFKFB2 expression was increased 4.7-fold in PE compared to NP (p < 0.001). PFKFB2 phosphorylation at Ser483 was increased 2.6-fold in PE compared to NP (p = 0.002). Expression of phosphorylated PFKFB2/PFKFB3 at Ser466/Ser461 was increased in PE, being present in 77.4% (95% CI 59.9–88.9%) of PE and 8.3% (95% CI 1.2–27.0%) of NP samples (p < 0.001). PFKFB3 was more commonly expressed in PE, detected in 90.3% (95% CI 74.3–97.4%) of PE and 8.3% (95% CI 1.2–27.0%) of NP samples (p < 0.001). PFKFB4 had a 7.2-fold increase in expression in PE compared to NP (p < 0.001). No significant differences between NP and NC groups were observed. Conclusion Regulatory proteins that increase glycolysis are increased in the urinary exosomes of subjects with pre-eclampsia, suggesting that renal glycolysis may be increased in this condition. |
| first_indexed | 2024-12-22T16:33:12Z |
| format | Article |
| id | doaj.art-61f750a8d91940499e3080afaff37142 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-22T16:33:12Z |
| publishDate | 2019-02-01 |
| publisher | BMC |
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| series | Journal of Translational Medicine |
| spelling | doaj.art-61f750a8d91940499e3080afaff371422022-12-21T18:20:01ZengBMCJournal of Translational Medicine1479-58762019-02-0117111010.1186/s12967-019-1806-6Increased expression and phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoforms in urinary exosomes in pre-eclampsiaR. Ellis0M. Katerelos1S. W. Choy2N. Cook3M. Lee4K. Paizis5G. Pell6S. Walker7D. A. Power8P. F. Mount9Faculty of Medicine, Dentistry and Health Sciences, University of MelbourneDepartment of Nephrology, Austin HealthDepartment of Nephrology, Austin HealthDepartment of Nephrology, Austin HealthFaculty of Medicine, Dentistry and Health Sciences, University of MelbourneDepartment of Nephrology, Austin HealthMercy Hospital for WomenMercy Hospital for WomenFaculty of Medicine, Dentistry and Health Sciences, University of MelbourneFaculty of Medicine, Dentistry and Health Sciences, University of MelbourneAbstract Background Glycolysis is altered in various kidney diseases, but little is known about glycolysis in pre-eclampsia, a multi-system disorder with major pathological effects on the kidney. Urinary exosomes provide a non-invasive alternative for studying changes in kidney metabolism. This study aims to characterise the expression and phosphorylation of isozymes of the key glycolytic regulatory protein, 6-phosphofructokinase-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2), in urinary exosomes of subjects with pre-eclampsia (PE), compared to normotensive non-pregnant (NC) and normotensive pregnant (NP) controls. Methods A cross-sectional study of NC (n = 19), NP (n = 23) and PE (n = 29) subjects was performed. Exosomes were isolated from urine samples by differential ultracentrifugation, and then analyzed by Western blot and densitometry for expression of PFK-2/FBPase-2 isozymes (PFKFB2, PFKFB3 and PFKFB4) and phosphorylation of PFKFB2 at residues Ser483 and Ser466 and PFKFB3 at Ser461. Results PFKFB2 expression was increased 4.7-fold in PE compared to NP (p < 0.001). PFKFB2 phosphorylation at Ser483 was increased 2.6-fold in PE compared to NP (p = 0.002). Expression of phosphorylated PFKFB2/PFKFB3 at Ser466/Ser461 was increased in PE, being present in 77.4% (95% CI 59.9–88.9%) of PE and 8.3% (95% CI 1.2–27.0%) of NP samples (p < 0.001). PFKFB3 was more commonly expressed in PE, detected in 90.3% (95% CI 74.3–97.4%) of PE and 8.3% (95% CI 1.2–27.0%) of NP samples (p < 0.001). PFKFB4 had a 7.2-fold increase in expression in PE compared to NP (p < 0.001). No significant differences between NP and NC groups were observed. Conclusion Regulatory proteins that increase glycolysis are increased in the urinary exosomes of subjects with pre-eclampsia, suggesting that renal glycolysis may be increased in this condition.http://link.springer.com/article/10.1186/s12967-019-1806-6Pre-eclampsiaGlycolysisUrinary exosomes6-Phosphofructo-2-kinase/fructose-26-BisphosphatasePhosphorylation |
| spellingShingle | R. Ellis M. Katerelos S. W. Choy N. Cook M. Lee K. Paizis G. Pell S. Walker D. A. Power P. F. Mount Increased expression and phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoforms in urinary exosomes in pre-eclampsia Journal of Translational Medicine Pre-eclampsia Glycolysis Urinary exosomes 6-Phosphofructo-2-kinase/fructose-2 6-Bisphosphatase Phosphorylation |
| title | Increased expression and phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoforms in urinary exosomes in pre-eclampsia |
| title_full | Increased expression and phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoforms in urinary exosomes in pre-eclampsia |
| title_fullStr | Increased expression and phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoforms in urinary exosomes in pre-eclampsia |
| title_full_unstemmed | Increased expression and phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoforms in urinary exosomes in pre-eclampsia |
| title_short | Increased expression and phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoforms in urinary exosomes in pre-eclampsia |
| title_sort | increased expression and phosphorylation of 6 phosphofructo 2 kinase fructose 2 6 bisphosphatase isoforms in urinary exosomes in pre eclampsia |
| topic | Pre-eclampsia Glycolysis Urinary exosomes 6-Phosphofructo-2-kinase/fructose-2 6-Bisphosphatase Phosphorylation |
| url | http://link.springer.com/article/10.1186/s12967-019-1806-6 |
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