Nitric oxide facilitates NFAT-dependent transcription in mouse myotubes

Drenning, J; Lira, Vitor A.; Simmons, Catherine; Soltow, Quinlyn A.; Sellman, Jeff E.; Criswell, David S.

doi:10.1152/ajpcell.00523.2007

Cited by 61 publications

(48 citation statements)

References 28 publications

(53 reference statements)

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“…41 A link between NO activity and UMOD expression was confirmed in wild-type mice exposed to a nonselective NOS inhibitor (L-NAME), which resulted in reduced UMOD protein expression in kidney tissue and urine. Of note, NO exerts regulatory control over two transcription factors-nuclear factor of activated T cells 42 and Oct-1 43 -both of which have consensus-binding sites in the promoter region of UMOD. 44 These observations raise the possibility of direct regulation of UMOD expression by NO, a suggestion that certainly warrants further study.…”

Section: Discussionmentioning

confidence: 99%

Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage

Tomlinson

Caplin

Boruc

et al. 2015

Journal of the American Society of Nephrology

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Nitric oxide (NO) production is diminished in many patients with cardiovascular and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, and elevated plasma levels of ADMA are associated with poor outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylargininemetabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1 gene variant associated with increased renal DDAH1 mRNA transcription and lower plasma ADMA levels, but counterintuitively, a steeper rate of renal function decline. Here, we test the hypothesis that reduced renal-specific ADMA metabolism protects against progressive renal damage. Renal DDAH1 is expressed predominately within the proximal tubule. A novel proximal tubule-specific Ddah1 knockout (Ddah1) mouse demonstrated tubular cell accumulation of ADMA and lower NO concentrations, but unaltered plasma ADMA concentrations. Ddah1 PT2/2 mice were protected from reduced kidney tissue mass, collagen deposition, and profibrotic cytokine expression in two independent renal injury models: folate nephropathy and unilateral ureteric obstruction. Furthermore, a study of two independent kidney transplant cohorts revealed higher levels of human renal allograft methylargininemetabolizing enzyme gene expression associated with steeper function decline. We also report an association among DDAH1 expression, NO activity, and uromodulin expression supported by data from both animal and human studies, raising the possibility that kidney DDAH1 expression exacerbates renal injury through uromodulinrelated mechanisms. Together, these data demonstrate that reduced renal tubular ADMA metabolism protects against progressive kidney function decline. Thus, circulating ADMA may be an imprecise marker of renal methylarginine metabolism, and therapeutic ADMA reduction may even be deleterious to kidney function.

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Section: Discussionmentioning

confidence: 99%

Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage

Tomlinson

Caplin

Boruc

et al. 2015

Journal of the American Society of Nephrology

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“…The activity of this enzyme can be inhibited with a high content of nitrogen oxide in the fiber, which acts through the guanylate cyclase mechanism [78]. We have previously shown that the nitrogen oxide level in rat soleus is significantly reduced during gravitational unloading [79].…”

Section: Expression Of Myosin Genes Under Conditions Of Gravitationalmentioning

confidence: 99%

From Slow to Fast: Hypogravity-Induced Remodeling of Muscle Fiber Myosin Phenotype

2016

Acta Naturae

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Skeletal muscle consists of different fiber types arranged in a mosaic pattern. These fiber types are characterized by specific functional properties. Slow-type fibers demonstrate a high level of fatigue resistance and prolonged contraction duration, but decreased maximum contraction force and velocity. Fast-type fibers demonstrate high contraction force and velocity, but profound fatigability. During the last decades, it has been discovered that all these properties are determined by the predominance of slow or fast myosin-heavy-chain (MyHC) isoforms. It was observed that gravitational unloading during space missions and simulated microgravity in ground-based experiments leads to the transformation of some slow-twitch muscle fibers into fast-twitch ones due to changes in the patterns of MyHC gene expression in the postural soleus muscle. The present review covers the facts and mechanistic speculations regarding myosin phenotype remodeling under conditions of gravitational unloading. The review considers the neuronal mechanisms of muscle fiber control and molecular mechanisms of regulation of myosin gene expression, such as inhibition of the calcineurin/NFATc1 signaling pathway, epigenomic changes, and the behavior of specific microRNAs. In the final portion of the review, we discuss the adaptive role of myosin phenotype transformations.

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“…Several studies suggest a role of endogenous NO in AMPKand Ca 2ϩ -dependent regulation of PGC-1␣, GLUT4, and mitochondrial genes (119,128). NO is also required for functional overload-induced upregulation of slow myosin heavy chain (MHC; type 1/␤) (182) through modulation of Akt and glycogen synthase kinase-3␤ (GSK-3␤) activities and amplification of CnA/NFAT-dependent signaling (51). In support of this, eNOS Ϫ/Ϫ muscle cells have reduced type 1 MHC expression (52), and low levels of NO donors promote mitochondrial biogenesis, PGC-1␣, and GLUT4 expression in cultured muscle cells (119,145) through a mechanism involving AMPK␣1 activation (Lira VA and Criswell DS, unpublished data).…”

Section: Pgc-1␣ Regulation In Response To Exercisementioning

confidence: 99%

PGC-1α regulation by exercise training and its influences on muscle function and insulin sensitivity

Lira

Benton

Yan

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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338

292

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Lira VA, Benton CR, Yan Z, Bonen A. PGC-1␣ regulation by exercise training and its influences on muscle function and insulin sensitivity. Am J Physiol Endocrinol Metab 299: E145-E161, 2010. First published April 6, 2010; doi:10.1152/ajpendo.00755.2009.-The peroxisome proliferator-activated receptor-␥ (PPAR␥) coactivator-1␣ (PGC-1␣) is a major regulator of exercise-induced phenotypic adaptation and substrate utilization. We provide an overview of 1) the role of PGC-1␣ in exercise-mediated muscle adaptation and 2) the possible insulin-sensitizing role of PGC-1␣. To these ends, the following questions are addressed. 1) How is PGC-1␣ regulated, 2) what adaptations are indeed dependent on PGC-1␣ action, 3) is PGC-1␣ altered in insulin resistance, and 4) are PGC-1␣-knockout and -transgenic mice suitable models for examining therapeutic potential of this coactivator? In skeletal muscle, an orchestrated signaling network, including Ca 2ϩ -dependent pathways, reactive oxygen species (ROS), nitric oxide (NO), AMP-dependent protein kinase (AMPK), and p38 MAPK, is involved in the control of contractile protein expression, angiogenesis, mitochondrial biogenesis, and other adaptations. However, the p38␥ MAPK/PGC-1␣ regulatory axis has been confirmed to be required for exercise-induced angiogenesis and mitochondrial biogenesis but not for fiber type transformation. With respect to a potential insulinsensitizing role of PGC-1␣, human studies on type 2 diabetes suggest that PGC-1␣ and its target genes are only modestly downregulated (Յ34%). However, studies in PGC-1␣-knockout or PGC-1␣-transgenic mice have provided unexpected anomalies, which appear to suggest that PGC-1␣ does not have an insulin-sensitizing role. In contrast, a modest (ϳ25%) upregulation of PGC-1␣, within physiological limits, does improve mitochondrial biogenesis, fatty acid oxidation, and insulin sensitivity in healthy and insulin-resistant skeletal muscle. Taken altogether, there is substantial evidence that the p38␥ MAPK-PGC-1␣ regulatory axis is critical for exerciseinduced metabolic adaptations in skeletal muscle, and strategies that upregulate PGC-1␣, within physiological limits, have revealed its insulin-sensitizing effects. endurance exercise; angiogenesis; mitochondria; fatty acid metabolism; glucose SKELETAL MUSCLE IS HIGHLY ADAPTABLE to changes in contractile activity and to changes in the substrate/endocrine milieu. Although the molecular bases for these adaptive responses had remained uncertain for many years, the peroxisome proliferator-activated receptor-␥ (PPAR␥) coactivator 1␣ (PGC-1␣) has revealed itself to be a major regulator of exercise-induced phenotypic adaptation and substrate utilization. In the present paper, we provide an overview and perspective on the mechanisms by which PGC-1␣ is regulated by endurance exercise training as well as on the influence of PGC-1␣ on fiber type transformation, angiogenesis, mitochondrial biogenesis, lipid metabolism, and insulin sensitivity.The first part of this review examines 1) the pathways involved...

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Nitric oxide facilitates NFAT-dependent transcription in mouse myotubes

Cited by 61 publications

References 28 publications

Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage

Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage

From Slow to Fast: Hypogravity-Induced Remodeling of Muscle Fiber Myosin Phenotype

PGC-1α regulation by exercise training and its influences on muscle function and insulin sensitivity

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