| AMP-activated protein kinase regulates lymphocyte responses to metabolic stress but is largely dispensable for immune cell development and function. | |
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MedLine Citation:
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PMID: 18350549 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AMP-activated protein kinase (AMPK), a phylogenetically conserved serine/threonine protein kinase, represents an energy sensor able to adapt cellular metabolism in response to nutritional environmental variations. TCR stimulation activates AMPK, a regulatory event that is known to stimulate ATP-producing processes, possibly in anticipation of the increased energetic needs associated with cell division and expression of effector function. Taking advantage of the selective expression of the AMPKalpha1 catalytic subunit in lymphoid cells, we have analyzed the in vitro and in vivo capacity of lymphocytes lacking AMPK activity (AMPKalpha1-KO cells) to respond to metabolic stress and to initiate and sustain an immune response. AMPKalpha1-KO cells displayed increasing sensitivity to energetic stress in vitro, and were found unable to maintain adequate ATP levels in response to ATP synthase inhibition. These cells were, however, able to respond to antigen stimulation in vitro, as shown by optimal proliferation and cytokine production. Similarly, AMPKalpha1-KO mice were fully immunocompetent in vivo and displayed normal cell proliferation, humoral, cytotoxic and delayed-type hypersensitivity (DTH) responses following antigen injection. In conclusion, AMPK represents an important enzyme allowing lymphocytes to resist a mild energy crisis in vitro, but is largely dispensable for activation and expression of effector function in response to antigen stimulation. |
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Authors:
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Alice Mayer; Sébastien Denanglaire; Benoit Viollet; Oberdan Leo; Fabienne Andris |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of immunology Volume: 38 ISSN: 0014-2980 ISO Abbreviation: Eur. J. Immunol. Publication Date: 2008 Apr |
Date Detail:
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Created Date: 2008-04-16 Completed Date: 2008-06-10 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 1273201 Medline TA: Eur J Immunol Country: Germany |
Other Details:
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Languages: eng Pagination: 948-56 Citation Subset: IM |
Affiliation:
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Laboratoire de Physiologie Animale, Université Libre de Bruxelles, Gosselies, Belgium. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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AMP-Activated Protein Kinases Animals Cell Proliferation Cells, Cultured Cytokines / immunology, secretion Lymphocytes / cytology, immunology*, metabolism*, secretion Mice Mice, Inbred C57BL Mice, Knockout Multienzyme Complexes / deficiency, genetics, metabolism* Protein-Serine-Threonine Kinases / deficiency, genetics, metabolism* Sensitivity and Specificity |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Multienzyme Complexes; EC 2.7.11.1/AMP-Activated Protein Kinases; EC 2.7.11.1/Protein-Serine-Threonine Kinases |
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