The familial Parkinson's disease gene DJ-1 (PARK7) is expressed in red cells and plays a role in protection against oxidative damage
| Autor: | Florent M. Martin, Jeffrey S. Friedman, Xiuling Xu |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Erythrocytes
Cell Survival Reticulocytosis Protein Deglycase DJ-1 SOD2 Mitochondrion medicine.disease_cause Article Superoxide dismutase Mice Superoxides Cell Line Tumor hemic and lymphatic diseases medicine Animals Molecular Biology Erythroid Precursor Cells Mice Knockout Oncogene Proteins chemistry.chemical_classification Reactive oxygen species biology Superoxide Dismutase Gene Expression Profiling PARK7 Peroxiredoxins Cell Biology Hematology Molecular biology Mitochondria Up-Regulation Oxidative Stress chemistry biology.protein Molecular Medicine medicine.symptom Oxidative stress |
| Zdroj: | Blood Cells, Molecules, and Diseases. 45:227-232 |
| ISSN: | 1079-9796 |
| DOI: | 10.1016/j.bcmd.2010.07.014 |
| Popis: | The antioxidant enzyme manganese superoxide dismutase (SOD2) serves as the primary defense against mitochondrial superoxide. Impaired SOD2 activity in murine hematopoietic cells affects erythroid development, resulting in anemia characterized by intra-mitochondrial iron deposition, reticulocytosis and shortened red cell life span. Gene expression profiling of normal and SOD2 deficient erythroblasts identified the Parkinson's disease locus DJ-1 (Park7) as a differentially expressed transcript. To investigate the role of DJ-1 in hematopoietic cell development and protection against oxidative stress caused by Sod2 loss, we evaluated red cell parameters, reticulocyte count, red cell turnover and reactive oxygen species production in DJ-1 knockout animals and chimeric animals lacking both SOD2 and DJ-1 in hematopoietic cells generated by fetal liver transplantation. We also investigated DJ-1 protein expression in primary murine erythroid and erythroleukemia cells (MEL). Loss of DJ-1 exacerbates the phenotype of SOD2 deficiency, increasing reticulocyte count and decreasing red cell survival. Using MEL cells, we show that DJ-1 is up-regulated at the protein level during erythroid differentiation. These results indicate that DJ-1 plays a physiologic role in protection of erythroid cells from oxidant damage, a function unmasked in the context of oxidative stress. |
| Databáze: | OpenAIRE |
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