Suppression of 5′-Nucleotidase Enzymes Promotes AMP-activated Protein Kinase (AMPK) Phosphorylation and Metabolism in Human and Mouse Skeletal Muscle

Kulkarni, Sameer S.; Karlsson, Håkan K.R.; Szekeres, Ferenc; Chibalin, Alexander V.; Krook, Anna; Zierath, Juleen R.

doi:10.1074/jbc.m111.268292

Cited by 69 publications

(69 citation statements)

References 47 publications

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“…These enzymes regulate the balance of intracellular nucleotide pools and probably play crucial roles in energy balance, metabolism regulation, and cell replication (13,14). Of note, one member of the 5′-nucleotidase family, NT5C1A, was recently shown to be a prevalent target of the immune response in IBM, but not in PM (5,6).…”

Section: Discussionmentioning

confidence: 99%

Cytosolic 5′‐Nucleotidase 1A As a Target of Circulating Autoantibodies in Autoimmune Diseases

Lloyd

Christopher‐Stine

Pinal‐Fernandez

et al. 2015

Arthritis Care & Research

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Objective Prior investigations demonstrated that autoantibodies recognizing cytosolic 5′-nucleotidase 1A (NT5C1A) are found in 33–76% of patients with inclusion body myositis (IBM) but are observed only rarely in patients with polymyositis (PM). Thus, anti-NT5C1A may help distinguish IBM from PM. Although 4–21% of patients with dermatomyositis (DM) were shown to be anti-NT5C1A antibody positive, the clinical features of anti-NT5C1A–positive patients with DM have not been described. Furthermore, the prevalence of anti-NT5C1A antibodies in other rheumatic conditions has not been reported. This study was undertaken to define the prevalence and clinical features of anti-NT5C1A–positive patients with DM, PM, IBM, or other systemic autoimmune diseases. Methods We screened for anti-NT5C1A autoantibodies in patients with IBM, DM, PM, Sjögren’s syndrome (SS), or systemic lupus erythematosus (SLE) and in healthy volunteers. Clinical characteristics were compared between patients who were anti-NT5C1A positive and those who were anti-NT5C1A negative. Results Anti-NT5C1A autoantibodies were detected in 71 (61%) of 117 patients with IBM, 2 (5%) of 42 patients with PM, 2 (5%) of 42 healthy volunteers, 24 (15%) of 159 patients with DM, 10 (23%) of 44 patients with SS, and 13 (14%) of 96 patients with SLE. No anti-NT5C1A antibody–positive patients with SS or SLE had muscle involvement. Anti-NT5C1A–positive patients with IBM had a lower prevalence of rimmed vacuoles (62% versus 83% of antibody-negative patients; P = 0.02). No differences in the clinical characteristics of antibody-positive and antibody-negative patients with DM, SS, or SLE were observed. Conclusion Anti-NT5C1A is a common target of circulating autoantibodies, especially in IBM but also in several different autoimmune diseases. In SLE and SS, anti-NT5C1A autoreactivity is not associated with muscle disease.

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Section: Discussionmentioning

confidence: 99%

Cytosolic 5′‐Nucleotidase 1A As a Target of Circulating Autoantibodies in Autoimmune Diseases

Lloyd

Christopher‐Stine

Pinal‐Fernandez

et al. 2015

Arthritis Care & Research

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“…Mitochondrial dysfunction and adenosine signaling could affect pain via activation of AMPK, a protein kinase heavily associated with pain plasticity [93]. Extracellular adenosine, increases in the AMP:ATP ratio during hypoxia, and inhibition of 5′NT all enhance AMPK activity [94,95,96,97]. It is possible that mitochondrial dysfunction within trigeminal pain processing brain regions exacerbates adenosinergic mechanisms and AMPK activity to produce headache.…”

Section: The Role Of Adenosine In Headache Pathophysiologymentioning

confidence: 99%

The Role of Adenosine Signaling in Headache: A Review

2017

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Migraine is the third most prevalent disease on the planet, yet our understanding of its mechanisms and pathophysiology is surprisingly incomplete. Recent studies have built upon decades of evidence that adenosine, a purine nucleoside that can act as a neuromodulator, is involved in pain transmission and sensitization. Clinical evidence and rodent studies have suggested that adenosine signaling also plays a critical role in migraine headache. This is further supported by the widespread use of caffeine, an adenosine receptor antagonist, in several headache treatments. In this review, we highlight evidence that supports the involvement of adenosine signaling in different forms of headache, headache triggers, and basic headache physiology. This evidence supports adenosine A2A receptors as a critical adenosine receptor subtype involved in headache pain. Adenosine A2A receptor signaling may contribute to headache via the modulation of intracellular Cyclic adenosine monophosphate (cAMP) production or 5' AMP-activated protein kinase (AMPK) activity in neurons and glia to affect glutamatergic synaptic transmission within the brainstem. This evidence supports the further study of adenosine signaling in headache and potentially illuminates it as a novel therapeutic target for migraine.

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“…AMP content is also determined in part by its degradation by AMP-deaminase and 5′-nucleotidase and inhibition of 5′-nucleotidase is emerging as a novel strategy to activate AMPK. 18 …”

Section: Molecular Mechanisms Of Ampk Activationmentioning

confidence: 99%

“…Knockdown of the AMP-degrading enzyme 5′-nucleotidase increases the AMP/ATP ratio, enhancing AMPK phosphorylation and the downstream activation of ACC and glucose transport in both myotubes and mouse skeletal muscle. 18 Although these results are of interest, the efficacy of inhibiting 5′-nucleotidase in the heart is not yet established and the potential sequelae of altering nucleotide metabolism warrant further consideration.…”

Section: Pharmacologic Ampk Activatorsmentioning

confidence: 99%

AMP-Activated Protein Kinase Regulation and Biological Actions in the Heart

Zaha¹,

Young²

2012

Circulation Research

234

188

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AMP-activated protein kinase (AMPK) is a stress-activated kinase that functions as a cellular fuel gauge and master metabolic regulator. Recent investigation has elucidated novel molecular mechanisms of AMPK regulation and important biological actions of the AMPK pathway that are highly relevant to cardiovascular disease. Activation of the intrinsic AMPK pathway plays an important role in the myocardial response to ischemia, pressure overload and heart failure. Pharmacologic activation of AMPK shows promise as a therapeutic strategy in the treatment of heart disease. The purpose of this review is to assess how recent discoveries have extended and in some cases challenged existing paradigms, providing new insights into the regulation of AMPK, its diverse biological actions and therapeutic potential in the heart.

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Suppression of 5′-Nucleotidase Enzymes Promotes AMP-activated Protein Kinase (AMPK) Phosphorylation and Metabolism in Human and Mouse Skeletal Muscle

Cited by 69 publications

References 47 publications

Cytosolic 5′‐Nucleotidase 1A As a Target of Circulating Autoantibodies in Autoimmune Diseases

Cytosolic 5′‐Nucleotidase 1A As a Target of Circulating Autoantibodies in Autoimmune Diseases

The Role of Adenosine Signaling in Headache: A Review

AMP-Activated Protein Kinase Regulation and Biological Actions in the Heart

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