AMPKalpha1 deletion shortens erythrocyte life span in mice: role of oxidative stress.
AMP-activated protein kinase (AMPK) is an energy sensor essential for maintaining cellular energy homeostasis. Here, we report that AMPKalpha1 is the predominant isoform of AMPK in murine erythrocytes and mice globally deficient in AMPKalpha1 (AMPKalpha1(-/-)), but not in those lacking AMPKalpha2, and the mice had markedly enlarged spleens with dramatically increased proportions of Ter119-positive erythroid cells. Blood tests revealed significantly decreased erythrocyte and hemoglobin levels with increased reticulocyte counts and elevated plasma erythropoietin concentrations in AMPKalpha1(-/-) mice. The life span of erythrocytes from AMPKalpha1(-/-) mice was less than that in wild-type littermates, and the levels of reactive oxygen species and oxidized proteins were significantly increased in AMPKalpha1(-/-) erythrocytes. In keeping with the elevated oxidative stress, treatment of AMPKalpha1(-/-) mice with the antioxidant, tempol, resulted in decreased reticulocyte counts and improved erythrocyte survival. Furthermore, the expression of Foxo3 and reactive oxygen species scavenging enzymes was significantly decreased in erythroblasts from AMPKalpha1(-/-) mice. Collectively, these results establish an essential role for AMPKalpha1 in regulating oxidative stress and life span in erythrocytes.
Wang
Shaobin
S
Division of Endocrinology and Diabetes, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104, USA.
Dale
George L
GL
Song
Ping
P
Viollet
Benoit
B
Zou
Ming-Hui
MH
D055372:AMP-Activated Protein Kinases / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D004906:Erythrocyte Count; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004921:Erythropoietin / Q000097:blood / Q000378:metabolism; D005434:Flow Cytometry; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression; D051379:Mice; D018345:Mice, Knockout; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010659:Phenylhydrazines / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000097:blood / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013163:Splenomegaly / Q000201:enzymology / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D013997:Time Factors; D000099156:Superoxide Dismutase 2
D055372:AMP-Activated Protein Kinases; D004921:Erythropoietin; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D016877:Oxidants; D010659:Phenylhydrazines; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C474033:FoxO3 protein, mouse; C030299:phenylhydrazine; C548179:Prkaa1 protein, mouse; C534978:Prkaa2 protein, mouse
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