Regulation of erythrocyte survival by AMP‐activated protein kinase
| Autor: | Erwin Schleicher, Kan Wang, Saisudha Koka, Hasan Mahmud, Florian Lang, Thomas Münzel, Shuchen Gu, Elisa Floride, Eberhard Schulz, Michael Föller, Mentor Sopjani |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Erythrocytes Phosphatidylserines AMP-Activated Protein Kinases Mitogen-activated protein kinase kinase Biochemistry Mice Cytosol AMP-activated protein kinase Phospholipid scrambling Genetics Animals Humans Annexin A5 Protein kinase A Molecular Biology Protein kinase B Cell Size Fluorescent Dyes Ionophores biology Chemistry Ionomycin Erythrocyte Membrane Cyclin-dependent kinase 2 AMPK Erythrocyte Aging Ribonucleotides Aminoimidazole Carboxamide Mice Mutant Strains Cell biology Glucose Pyrimidines biology.protein Pyrazoles Calcium cGMP-dependent protein kinase Fluorescein-5-isothiocyanate Biotechnology |
| Zdroj: | The FASEB Journal. 23:1072-1080 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.08-121772 |
| Popis: | AMP-activated protein kinase (AMPK), an energy-sensing enzyme, counteracts energy depletion by stimulation of energy production and limitation of energy utilization. On energy depletion, erythrocytes undergo suicidal death or eryptosis, triggered by an increase in cytosolic Ca(2+) activity ([Ca(2+)](i)) and characterized by cell shrinkage and phosphatidylserine (PS) exposure at the erythrocyte surface. The present study explored whether AMPK participates in the regulation of eryptosis. Western blotting and confocal microscopy disclosed AMPK expression in erythrocytes. [Ca(2+)](i) (Fluo3 fluorescence), cell volume (forward scatter), and PS exposure (annexin V binding) were determined by fluorescence-activated cell sorting (FACS) analysis. Glucose removal increased [Ca(2+)](i), decreased cell volume, and increased PS exposure. The AMPK-inhibitor compound C (20 microM) did not significantly modify eryptosis under glucose-replete conditions but significantly augmented the eryptotic effect of glucose withdrawal. An increase in [Ca(2+)](i) by Ca(2+) ionophore ionomycin triggered eryptosis, an effect blunted by the AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR; 1 mM). As compared with erythrocytes from wild-type littermates (ampk(+/+)), erythrocytes from AMPKalpha1-deficient mice (ampk(-/-)) were significantly more susceptible to the eryptotic effect of energy depletion. The ampk(-/-) mice were anemic despite excessive reticulocytosis, and they suffered from severe splenomegaly, again pointing to enhanced erythrocyte turnover. The observations disclose a critical role of AMPK in the survival of circulating erythrocytes. |
| Databáze: | OpenAIRE |
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