AMPKα1 Deletion Shortens Erythrocyte Life Span in Mice

Wang, Shaobin; Dale, George L.; Song, Ping; Viollet, Benoı̂t; Zou, Ming‐Hui

doi:10.1074/jbc.m110.102467

Cited by 89 publications

(67 citation statements)

References 46 publications

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“…1 Removal of senescent RBC (sRBC) from the circulation occurs through phagocytosis (erythrophagocytosis, EPC), which takes place mainly in macrophages of the spleen, but also in the liver and the bone marrow. 2 Macrophages recognize sRBC by a range of senescence markers.…”

Section: Introductionmentioning

confidence: 99%

Physiologically aged red blood cells undergo erythrophagocytosis in vivo but not in vitro

Gottlieb¹,

Topaz²,

Cohen³

et al. 2012

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundThe lifespan of red blood cells is terminated when macrophages remove senescent red blood cells by erythrophagocytosis. This puts macrophages at the center of systemic iron recycling in addition to their functions in tissue remodeling and innate immunity. Thus far, erythrophagocytosis has been studied by evaluating phagocytosis of erythrocytes that were damaged to mimic senescence. These studies have demonstrated that acquisition of some specific individual senescence markers can trigger erythrophagocytosis by macrophages, but we hypothesized that the mechanism of erythrophagocytosis of such damaged erythrocytes might differ from erythrophagocytosis of physiologically aged erythrocytes. Design and MethodsTo test this hypothesis we generated an erythrocyte population highly enriched in senescent erythrocytes by a hypertransfusion procedure in mice. Various erythrocyte-aging signals were analyzed and erythrophagocytosis was evaluated in vivo and in vitro. ResultsThe large cohort of senescent erythrocytes from hypertransfused mice carried numerous aging signals identical to those of senescent erythrocytes from control mice. Phagocytosis of fluorescently-labeled erythrocytes from hypertransfused mice injected into untreated mice was much higher than phagocytosis of labeled erythrocytes from control mice. However, neither erythrocytes from hypertransfused mice, nor those from control mice were phagocytosed in vitro by primary macrophage cultures, even though these cultures were able to phagocytose oxidatively damaged erythrocytes. ConclusionsThe large senescent erythrocyte population found in hypertransfused mice mimics physiologically aged erythrocytes. For effective erythrophagocytosis of these senescent erythrocytes, macrophages depend on some features of the intact phagocytosing tissue for support. ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n

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Section: Introductionmentioning

confidence: 99%

Physiologically aged red blood cells undergo erythrophagocytosis in vivo but not in vitro

Gottlieb¹,

Topaz²,

Cohen³

et al. 2012

Haematologica

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show abstract

“…We previously reported that AMPK␣1 is required for erythrocyte survival (25) and that AMPK is important for the survival of endothelial cells under conditions of hypoxia and energy deprivation (26). Here, we use a genetically modified cellular model to investigate the roles of AMPK in the genotoxic stress response.…”

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confidence: 99%

Inhibition of AMP-activated Protein Kinase α (AMPKα) by Doxorubicin Accentuates Genotoxic Stress and Cell Death in Mouse Embryonic Fibroblasts and Cardiomyocytes

Wang

Song

2012

Journal of Biological Chemistry

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“…AMPK, an important energy sensor in cells, also plays an important role in cell survival/ death by regulating H 2 O 2 , previous studies demonstrated that activation of AMPK significantly reduced hydrogen peroxide induced necrosis and cell death in mouse primary culture hepatocyte and H9c2 cells respectively, and inhibition of AMPK promote hydrogen peroxide induced necrosis and cell death [23,24]. Moreover, the levels of ROS significantly increased in AMPK deficiency mice [25]. The APAP-induced and Nrf2-regulated genes therefore might have very different roles in bioactivation, detoxification and antioxidative defense.…”

Section: Discussionmentioning

confidence: 98%

Overexpression of Aldose Reductase Render Mouse Hepatocytes More Sensitive to Acetaminophen Induced Oxidative Stress and Cell Death

Ahmed

Al-Obosi²,

Osman

et al. 2015

Ind J Clin Biochem

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Acetaminophen (APAP) a commonly used drug for decrease the fever and pain but is capable to induced hepatotoxicity at over dose. This study was carried out to investigate the effect of APAP on the expression of antiapoptotic and antioxidative defense genes, and whether aldose reductase over-expressing plasmid capable to protect against APAP-induced oxidative stress and cell death. APAP treatment induced oxidative stress and hepatotoxicity, and significantly increased aldose reductase mRNA and protein expression in mouse hepatocyte (AML-12).Unexpectedly, AML-12 cells over-expressing aldose reductase augmented APAP-induced reduction in cell viability, reactive oxygen species (ROS) production, glutathione (GSH) depletion and glutathione S-transferase A2 expression. Moreover, over-expression of aldose reductase potentiated APAP induced reduction on proliferating cell nuclear antigen, B cell lymphoma-extra large (bcl-x L ), catalase, glutathione peroxidase-1 (GPx-1) and abolished APAP-induced B-cell lymphoma 2 (bcl-2) inductions. Further, over-expression of aldose reductase significantly abolished AMP activated protein kinase (AMPK) activity in APAP-treated cells and induced p53 expression. This results demonstrate that APAP induced toxicity in AML-12, increased aldose reductase expression, and over-expression of aldose reductase render this cell more susceptible to APAP induced oxidative stress and cell death, this probably due to inhibition AMPK or bcl-2 activity, or may due to competition between aldose reductase and glutathione reductase for NADPH.

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AMPKα1 Deletion Shortens Erythrocyte Life Span in Mice

Cited by 89 publications

References 46 publications

Physiologically aged red blood cells undergo erythrophagocytosis in vivo but not in vitro

Physiologically aged red blood cells undergo erythrophagocytosis in vivo but not in vitro

Inhibition of AMP-activated Protein Kinase α (AMPKα) by Doxorubicin Accentuates Genotoxic Stress and Cell Death in Mouse Embryonic Fibroblasts and Cardiomyocytes

Overexpression of Aldose Reductase Render Mouse Hepatocytes More Sensitive to Acetaminophen Induced Oxidative Stress and Cell Death

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