title: Loss of AMPK exacerbates experimental autoimmune encephalomyelitis disease severity.
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). 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).
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, SC 29425, USA.
authors.forename: Narender
authors.initials: N
authors.lastname: Nath
authors.forename: Musfiquidin
authors.initials: M
authors.lastname: Khan
authors.forename: Ramandeep
authors.initials: R
authors.lastname: Rattan
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Mangalam
authors.forename: Randhir S
authors.initials: RS
authors.lastname: Makkar
authors.forename: Carloe
authors.initials: C
authors.lastname: de Meester
authors.forename: Luc
authors.initials: L
authors.lastname: Bertrand
authors.forename: Inderjit
authors.initials: I
authors.lastname: Singh
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Chen
authors.forename: Benoit
authors.initials: B
authors.lastname: Viollet
authors.forename: Shailendra
authors.initials: S
authors.lastname: Giri
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D015536:Down-Regulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology* / Q000473:pathology*; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D021122:Protein Subunits / Q000096:biosynthesis / Q000235:genetics; D013154:Spleen / Q000201:enzymology
chemical_list: D007527:Isoenzymes; D021122:Protein Subunits; D055372:AMP-Activated Protein Kinases