Loss of AMPK exacerbates experimental autoimmune encephalomyelitis disease severity

Narender Nath; Musfiquidin Khan; Ramandeep Rattan; Ashutosh Mangalam; Randhir S Makkar; Carloe de Meester; Luc Bertrand; Inderjit Singh; Yingjie Chen; Benoit Viollet; Shailendra Giri

doi:10.1016/j.bbrc.2009.05.106

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Loss of AMPK exacerbates experimental autoimmune encephalomyelitis disease severity

Journal article

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Peer reviewed

Loss of AMPK exacerbates experimental autoimmune encephalomyelitis disease severity

Narender Nath, Musfiquidin Khan, Ramandeep Rattan, Ashutosh Mangalam, Randhir S Makkar, Carloe de Meester, Luc Bertrand, Inderjit Singh, Yingjie Chen, Benoit Viollet, …

Biochemical and Biophysical Research Communications, Vol.386(1), pp.16-20

08/14/2009

DOI: 10.1016/j.bbrc.2009.05.106

PMCID: PMC2976596

PMID: 19486896

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https://www.ncbi.nlm.nih.gov/pmc/articles/2976596View

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Abstract

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). AMPKα1 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 AMPKα1 null mice (−/−) using MOG35–55 peptide. AMPKα1−/− mice exhibited severe EAE disease with profound infiltration of mononuclear cells compared to wild type mice however, AMPKα2 is not involved in enhancing the severity of the disease. Spleen cells isolated from AMPKα1−/− immunized mice exhibited a significant induction in the production of IFNγ. 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).

EAE

AMPK

Multiple sclerosis

T cells

Macrophage

Details

Title: Subtitle: Loss of AMPK exacerbates experimental autoimmune encephalomyelitis disease severity
Creators: Narender Nath - Department of Pediatrics, Medical University of South Carolina, SC 29425, USA
Musfiquidin Khan - Department of Pediatrics, Medical University of South Carolina, SC 29425, USA
Ramandeep Rattan - Department of Experimental Pathology, Mayo Clinic, Rochester, MN 55902, USA
Ashutosh Mangalam - Department of Immunology, Mayo Clinic, Rochester, MN 55902, USA
Randhir S Makkar - Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA
Carloe de Meester - Université catholique de Louvain, Division of Cardiology, School of Medicine, Brussels, Belgium
Luc Bertrand - Université catholique de Louvain, Division of Cardiology, School of Medicine, Brussels, Belgium
Inderjit Singh - Department of Pediatrics, Medical University of South Carolina, SC 29425, USA
Yingjie Chen - Division of Cardiovascular and Center for Vascular Biology, University of Minnesota, Minneapolis, MN 55455, USA
Benoit Viollet - Institut Cochin, Université René Descartes, Centre National de la Recherche Scientifique (UMR 8104), Paris, France
Shailendra Giri - Department of Pediatrics, Medical University of South Carolina, SC 29425, USA
Resource Type: Journal article
Publication Details: Biochemical and Biophysical Research Communications, Vol.386(1), pp.16-20
DOI: 10.1016/j.bbrc.2009.05.106
PMID: 19486896
PMCID: PMC2976596
NLM abbreviation: Biochem Biophys Res Commun
ISSN: 0006-291X
eISSN: 1090-2104
Publisher: Elsevier Inc
Language: English
Date published: 08/14/2009
Academic Unit: Pathology; Iowa Neuroscience Institute
Record Identifier: 9983905643902771

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