Anti-glycophorin C induces mitochondrial membrane depolarization and a loss of extracellular regulated kinase 1/2 protein kinase activity that is prevented by pretreatment with cytochalasin D: implications for hemolytic disease of the fetus and newborn ca
| Autor: | Gregory A. Denomme, Jonathan A. Micieli, Duncheng Wang |
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| Rok vydání: | 2010 |
| Předmět: |
Membrane Potential
Mitochondrial Cytochalasin D Kinase Cell growth Immunology Infant Newborn Antibodies Monoclonal Depolarization Hematology Mitochondrion Biology Molecular biology Erythroblastosis Fetal chemistry.chemical_compound chemistry Humans Immunology and Allergy Cytochalasin Glycophorins Signal transduction Extracellular Signal-Regulated MAP Kinases K562 Cells Protein kinase A |
| Zdroj: | Transfusion. 50:1761-1765 |
| ISSN: | 0041-1132 |
| DOI: | 10.1111/j.1537-2995.2010.02640.x |
| Popis: | BACKGROUND: Anti-glycophorin C (GPC), blood group antibodies of which cause hemolytic disease of the fetus and newborn (HDFN), is a potent inhibitor of erythroid progenitor cell growth. The cellular mechanism for growth inhibition has not been characterized. STUDY DESIGN AND METHODS: K562 cells were incubated in the presence of either anti-GPC, an immunoglobulin G isotype control, an inhibitor of actin polymerization called cytochalasin D with anti-GPC, or cytochalasin D alone. The JC-1 cationic dye was used to detect mitochondrial depolarization and the activity of the mitogen-activated protein kinases was assessed by Western blotting. RESULTS: Anti-GPC inhibits the activity of extracellular regulated kinase (ERK)1/2 within 10 minutes but does not alter the activity of p38 or c-Jun N-terminal kinase. After 24 hours there was a significant loss of mitochondrial membrane potential compared to isotype control–treated cells. Both the ERK1/2 inhibition and the loss of mitochondrial potential were prevented by pretreatment with cytochalasin D. CONCLUSION: A cell surface antibody can cause anemia by altering the signaling pathways in erythroid cells by promoting depolarization of mitochondria via cytoskeletal rearrangement. The observation that neonates with anti-GPC HDFN are unresponsive to erythropoietin can be explained by the antibody inhibiting a protein kinase through which this hematopoietic growth factor achieves its effects. |
| Databáze: | OpenAIRE |
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