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

Research output: Contribution to journalArticle

49 Scopus citations

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).

Original languageEnglish (US)
Pages (from-to)16-20
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume386
Issue number1
DOIs
StatePublished - Aug 14 2009

Keywords

  • AMPK
  • EAE
  • Macrophage
  • Multiple sclerosis
  • T cells

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Nath, N., Khan, M., Rattan, R., Mangalam, A., Makkar, R. S., Meester, C. D., Bertrand, L., Singh, I., Chen, Y., Viollet, B., & Giri, S. (2009). Loss of AMPK exacerbates experimental autoimmune encephalomyelitis disease severity. Biochemical and Biophysical Research Communications, 386(1), 16-20. https://doi.org/10.1016/j.bbrc.2009.05.106