RGD Reference Report - Loss of AMPK exacerbates experimental autoimmune encephalomyelitis disease severity. - Rat Genome Database

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Loss of AMPK exacerbates experimental autoimmune encephalomyelitis disease severity.

Authors: Nath, N  Khan, M  Rattan, R  Mangalam, A  Makkar, RS  De Meester, C  Bertrand, L  Singh, I  Chen, Y  Viollet, B  Giri, S 
Citation: Nath N, etal., Biochem Biophys Res Commun. 2009 Aug 14;386(1):16-20. Epub 2009 May 30.
RGD ID: 6484540
Pubmed: PMID:19486896   (View Abstract at PubMed)
PMCID: PMC2976596   (View Article at PubMed Central)
DOI: DOI:10.1016/j.bbrc.2009.05.106   (Journal Full-text)

AMP-activated protein kinase (AMPK) is an energy sensing metabolic switch in mammalian cells. Here, we report our novel finding that AMPK is lost in all immune cells of experimental autoimmune encephalomyelitis (EAE), an inflammatory disease of Central Nervous System (CNS). AMPKalpha1 is predominantly expressed in T cells and antigen presenting cells (APCs), which are primarily involved in EAE disease progression. AMPK is lost at protein level in spleen macrophages, total T cells and their subsets (CD4, CD8 and regulatory T cells) isolated from EAE afflicted animals compared to control, without affecting its mRNA levels suggesting that the loss of AMPK protein is the result of posttranscriptional modification. To examine its pathological relevance in inflammatory disease, EAE was induced in wild type (+/+) and AMPKalpha1 null mice (-/-) using MOG(35-55) peptide. AMPKalpha1(-/-) mice exhibited severe EAE disease with profound infiltration of mononuclear cells compared to wild type mice however, AMPKalpha2 is not involved in enhancing the severity of the disease. Spleen cells isolated from AMPKalpha1(-/-) immunized mice exhibited a significant induction in the production of IFNgamma. Our study identifies AMPK as a down regulated target during disease in all immune cells and possibly restoring AMPK may serve as a novel therapeutic target in autoimmune diseases like multiple sclerosis (MS).

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Autoimmune Encephalomyelitis severityISOPrkaa1 (Mus musculus)6484540; 6484540 RGD 
Experimental Autoimmune Encephalomyelitis severityIMP 6484540 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Prkaa1  (protein kinase AMP-activated catalytic subunit alpha 1)

Genes (Mus musculus)
Prkaa1  (protein kinase, AMP-activated, alpha 1 catalytic subunit)

Genes (Homo sapiens)
PRKAA1  (protein kinase AMP-activated catalytic subunit alpha 1)


Additional Information