Abstract:
AIM:Skeletal muscle nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathways are impaired in Duchenne and Becker muscular dystrophy partly because of reduced nNOSμ and soluble guanylate cyclase (GC) activity. However, GC function and the consequences of reduced GC activity in skeletal muscle are unknown. In this study, we explore the functions of GC and NO-cGMP signaling in skeletal muscle. RESULTS:GC1, but not GC2, expression was higher in oxidative than glycolytic muscles. GC1 was found in a complex with nNOSμ and targeted to nNOS compartments at the Golgi complex and neuromuscular junction. Baseline GC activity and GC agonist responsiveness was reduced in the absence of nNOS. Structural analyses revealed aberrant microtubule directionality in GC1-/- muscle. Functional analyses of GC1-/- muscles revealed reduced fatigue resistance and postexercise force recovery that were not due to shifts in type IIA-IIX fiber balance. Force deficits in GC1-/- muscles were also not driven by defects in resting mitochondrial adenosine triphosphate (ATP) synthesis. However, increasing muscle cGMP with sildenafil decreased ATP synthesis efficiency and capacity, without impacting mitochondrial content or ultrastructure. INNOVATION:GC may represent a new target for alleviating muscle fatigue and that NO-cGMP signaling may play important roles in muscle structure, contractility, and bioenergetics. CONCLUSIONS:These findings suggest that GC activity is nNOS dependent and that muscle-specific control of GC expression and differential GC targeting may facilitate NO-cGMP signaling diversity. They suggest that nNOS regulates muscle fiber type, microtubule organization, fatigability, and postexercise force recovery partly through GC1 and suggest that NO-cGMP pathways may modulate mitochondrial ATP synthesis efficiency. Antioxid. Redox Signal. 26, 966-985.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Moon Y,Balke JE,Madorma D,Siegel MP,Knowels G,Brouckaert P,Buys ES,Marcinek DJ,Percival JMdoi
10.1089/ars.2016.6630subject
Has Abstractpub_date
2017-06-10 00:00:00pages
966-985issue
17eissn
1523-0864issn
1557-7716journal_volume
26pub_type
杂志文章,评审abstract::The unfolded protein response (UPR) is an adaptive stress response in which cells recover from the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) by increasing its protein-folding capacity. The IRE1 pathway in the UPR is evolutionarily conserved from yeast to human, and two other path...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2007.1819
更新日期:2007-12-01 00:00:00
abstract:SIGNIFICANCE:Cardiovascular diseases are the main cause of death worldwide and pose an immense economical burden. In most cases, the underlying problem is vascular occlusion by atherosclerotic plaques. Importantly, different cell types of the vascular wall and the immune system play crucial roles in atherosclerosis at ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2016.6946
更新日期:2017-05-01 00:00:00
abstract::Peroxisomes are multifunctional organelles with an important role in the generation and decomposition of reactive oxygen species (ROS). In this review, the ROS-producing enzymes, as well as the antioxidative defense system in mammalian peroxisomes, are described. In addition, various conditions leading to disturbances...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2009.2996
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abstract::Chronic obstructive pulmonary disease (COPD) has recently been viewed as an inflammation-dependent systemic disease. Oxidative modifications in the pulmonary microenvironment can result in a number of functional changes in pulmonary tissue as well as in the blood. Studies have been carried out to detect whether oxidat...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2007.1864
更新日期:2008-04-01 00:00:00
abstract:AIMS:Oxidative stress is thought to be involved in Friedreich's ataxia (FRDA), yet it has not been demonstrated in the target neurons that are first to degenerate. Using the YG8R mouse model of FRDA, microarray and neuritic growth experiments were carried out in the dorsal root ganglion (DRG), the primary site of neuro...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.4537
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abstract::Hydrogen sulfide (H(2)S) is a gasotransmitter with multifaceted physiological functions, including the regulation of glucose metabolism. Methylglyoxal (MG) is an intermediate of glucose metabolism and plays an important role in the pathogenesis of insulin resistance syndromes. In the present study, we investigated the...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2009.2918
更新日期:2010-05-01 00:00:00
abstract::Oxidative stress due to increased epidermal levels of H(2)O(2) with consequent inhibition of catalase activity is generally accepted as a leading cytotoxic mechanism of melanocyte loss in vitiligo. Keratinocyte-derived cytokines are considered key factors in the maintenance of melanocyte structure and functions. We hy...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2009.2976
更新日期:2010-09-01 00:00:00
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2010.3780
更新日期:2011-07-15 00:00:00
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2008.2097
更新日期:2009-02-01 00:00:00
abstract:AIMS:Carbon monoxide (CO)-releasing molecules (CORMs) are candidates for animal and antimicrobial therapeutics. We aimed to probe the antimicrobial potential of a novel manganese CORM. RESULTS:[Mn(CO)4S2CNMe(CH2CO2H)], CORM-401, inhibits growth of Escherichia coli and several antibiotic-resistant clinical pathogens. C...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2017.7239
更新日期:2018-05-10 00:00:00
abstract:SIGNIFICANCE:Chagas disease (CD) affects several million people in Latin America and is spreading beyond its classical boundaries due to the migration of infected host and insect vectors, HIV co-infection, and blood transfusion. The current therapy is not adequate for treatment of the chronic phase of CD, and new drugs...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.4618
更新日期:2013-09-01 00:00:00
abstract:AIMS:Adenosine triphosphate (ATP) synthase uses chemiosmotic energy across the inner mitochondrial membrane to convert adenosine diphosphate and orthophosphate into ATP, whereas genetic deletion of Sirt3 decreases mitochondrial ATP levels. Here, we investigate the mechanistic connection between SIRT3 and energy homeost...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2013.5420
更新日期:2014-08-01 00:00:00
abstract::Monothiol glutaredoxins (Grxs) with a noncanonical CGFS active site are found in all kingdoms of life. They include members with a single domain and thioredoxin-Grx fusion proteins. In Saccharomyces cerevisiae, the multidomain Grx3 and Grx4 play an essential role in intracellular iron trafficking. This crucial task is...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2010.3811
更新日期:2011-07-01 00:00:00
abstract::Cellular redox balance is vital in health and disease. In this Forum, we highlight the importance of reactive oxygen species (ROS) in the regulation of redox balance in different organ systems of the body and ROS contribution to the development of hypertension. The Forum examines interactions between oxidative and nit...
journal_title:Antioxidants & redox signaling
pub_type: 社论
doi:10.1089/ars.2013.5591
更新日期:2014-01-01 00:00:00
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2010.3877
更新日期:2011-10-15 00:00:00
abstract::Peroxiredoxins (Prxs) are a family of peroxidases that reduce peroxides, with a conserved cysteine residue (the peroxidatic Cys) serving as the site of oxidation by peroxides. Peroxides oxidize the peroxidatic Cys-SH to Cys-SOH, which then reacts with another cysteine residue (typically the resolving Cys [C(R)]) to fo...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3393
更新日期:2011-08-01 00:00:00
abstract::The endothelium is essential for the maintenance of vascular homeostasis. Central to this role is the production of endothelium-derived nitric oxide (EDNO), synthesized by the endothelial isoform of nitric oxide synthase (eNOS). Endothelial dysfunction, manifested as impaired EDNO bioactivity, is an important early ev...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2008.2027
更新日期:2008-10-01 00:00:00
abstract:: Aims: The management of myocardial ischemia has been challenged by reperfusion injury. Reactive oxygen species (ROS) production is the critical cause of reperfusion injury, but antioxidant treatment failed to gain satisfactory effects. We hypothesized that improvement of r...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2018.7624
更新日期:2019-07-20 00:00:00
abstract:AIMS:Endothelium-dependent vasorelaxation is mediated by endothelium-derived relaxing factor and endothelium-derived hyperpolarizing factor (EDHF). However, the molecular entity of EDHF remains unclear. The present study examined whether hydrogen sulfide (H₂S) acts as EDHF and how H₂S mediates EDHF pathways from endoth...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.4805
更新日期:2013-11-10 00:00:00
abstract::It has been known that glutathione S-transferases (GSTs) can reduce lipid hydroperoxides through their Se-independent glutathione peroxidase activity and that these enzymes can also detoxify lipid peroxidation end products such as 4-hydroxynonenal (4-HNE). In this article, recent studies suggesting that the Alpha clas...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/152308604322899350
更新日期:2004-04-01 00:00:00
abstract::Cell division requires the coordinated assembly of cyclins and cyclin-dependent kinases that promote cell-cycle progression through S phase and mitosis. Two families of cyclin-dependent kinase inhibitors prevent abnormal or premature proliferation by blocking cyclin kinase activity. Expression of the cyclin-dependent ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2005.7.108
更新日期:2005-01-01 00:00:00
abstract:AIMS:Large doses of intraperitoneally injected basic amino acids, L-arginine, or L-ornithine, induce acute pancreatitis in rodents, although the mechanisms mediating pancreatic toxicity remain unknown. Another basic amino acid, L-lysine, was also shown to cause pancreatic acinar cell injury. The aim of the study was to...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2011.4065
更新日期:2011-11-15 00:00:00
abstract:AIMS:Heart failure (HF) is characterized by regionalized contractile alterations resulting in loss of the transmural contractile gradient across the left ventricular free wall. We tested whether a regional alteration in mitochondrial oxidative metabolism during HF could affect myofilament function through protein kinas...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.4534
更新日期:2013-03-20 00:00:00
abstract::Despite the significance of redox post-translational modifications (PTMs) in regulating diverse signal transduction pathways, the enzymatic systems that catalyze reversible and specific oxidative or reductive modifications have yet to be firmly established. Thioredoxin 1 (Trx1) is a conserved antioxidant protein that ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3831
更新日期:2011-11-01 00:00:00
abstract:AIMS:Recent studies have revealed that autophagy is induced under various disease conditions; however, the role of autophagy in pathological states is controversial. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a highly inducible cytoprotective gene that regulates reactive oxygen species (ROS) generation. In this study,...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2015.6386
更新日期:2016-05-20 00:00:00
abstract::Integrin-mediated phagocytosis in fibroblasts is associated to collagenase 1 induction when the particles are coated with high-affinity binding ligands. This study shows that the high density of ligand coating on the particle elicits RhoA-dependent particle uptake coupled to signal transduction. Integrin clustering in...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2005.7.318
更新日期:2005-03-01 00:00:00
abstract::Ceramide has been shown by many studies to induce apoptosis. Therefore, upregulation of ceramide is discussed as a novel approach for tumor treatment. However, it is unknown whether overexpression of acid sphingomyelinase releasing ceramide from sphingomyelin sensitizes cells to chemotherapy and, thus, serves as a pot...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2007.1673
更新日期:2007-09-01 00:00:00
abstract::Anthracyclines are widely used in anticancer protocols, but can induce cardiotoxicity by mechanisms that mainly involve oxidative damage and mitochondrial dysfunction. Radiotherapy (RT) can also impair cardiac function by promoting myocardial fibrosis, microvascular damage, and decreased density of myocardial capillar...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2019.7842
更新日期:2019-11-20 00:00:00
abstract::Dr. Gregg L. Semenza is recognized here as a Redox Pioneer because he has published three articles that have been cited more than 1,000 times, and 74 articles that have each been cited more than 100 times. Dr. Semenza is known for his seminal discovery of hypoxia-inducible factor-1 (HIF-1) and for identifying molecula...
journal_title:Antioxidants & redox signaling
pub_type: 传,历史文章,杂志文章
doi:10.1089/ars.2010.3155
更新日期:2010-08-15 00:00:00
abstract::Although oxygen is essential for promoting energy metabolism and for enhancing cell proliferation, early mouse embryos are very sensitive to high oxygen concentration. Because the tissue-specificity and sequential changes of the expression of antioxidative enzymes in rodent embryos have not been investigated systemati...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2000.2.4-653
更新日期:2000-01-01 00:00:00