Nitric oxide donors improve prednisone effects on muscular dystrophy in the<i>mdx</i>mouse diaphragm

Mizunoya, Wataru; Upadhaya, Ritika; Burczynski, Frank J.; Wang, Guqi; Anderson, Judy E.

doi:10.1152/ajpcell.00482.2010

Cited by 26 publications

(43 citation statements)

References 94 publications

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“…We therefore propose that combining exercise with an exogenous source of NO has potential as a method to combat age-related muscle atrophy. NO donors improved regeneration in mdx mouse diaphragm during prednisone treatment (52) and effects of nonsteroidal anti-inflammatory drugs on mdx mouse dystrophy and alpha-sarcoglycanopathy (11,64). By extension, therefore, since SC activation is a critical step in muscle regeneration, NO-based interventions very likely have strong potential to rescue the regenerative capacity of stem cells in aged muscle.…”

Section: Discussionmentioning

confidence: 97%

“…Double immunostaining for NOS-1 and ␤DG was performed using the IHC World protocol, which is a parallel approach (31) that employs multiple blocking steps including normal goat serum, the unconjugated Fab fragment of goat anti-rabbit or antimouse IgG, and avidin and biotin as reported (52). After blocking, sections were incubated in a mixture of two primary antibodies, rabbit polyclonal anti-NOS1 (sc-1025, Santa Cruz Biotechnology, 1:50) and mouse monoclonal anti-␤-dystroglycan (NCL-43DAG, Novocastra, 1:100) overnight at 4°C.…”

Section: Methodsmentioning

confidence: 99%

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Nitric oxide and voluntary exercise together promote quadriceps hypertrophy and increase vascular density in female 18-mo-old mice

Leiter

Upadhaya²,

Anderson

2012

American Journal of Physiology-Cell Physiology

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Age-related sarcopenia reduces the size, strength, and function of muscle, and the diameter of muscle fibers. It also disrupts the dystrophin-glycoprotein complex, dislocating nitric oxide synthase 1 (NOS-1) and reducing sarcolemmal integrity. This study of quadriceps muscle in 18-mo-old mice showed that NO-donor treatment with isosorbide dinitrate (I) for 6 wk, in combination with voluntary exercise for 3 wk, increased muscle mass by 25% and stimulated cell proliferation. The resulting fiber hypertrophy was accompanied by a lower ratio of protein:DNA, consistent with myogenic-cell hyperplasia. Treatment enhanced the ratio of NOS-1:β-dystroglycan in correlation with fiber diameter, improved sarcolemmal integrity, and increased vascular density after an increase in vascular endothelial growth factor protein at 3 wk. Results demonstrate that age-related muscle refractoriness to exercise can be overcome with NO-donor treatment. Since activation of muscle stem cells and vascular perfusion are limiting factors in the maintenance, regeneration, and growth of aged muscle, results suggest the feasibility of using NO-donor drugs to combat atrophy and muscle ischemia. Improved function and quality of life from the NO-amplified effects of exercise may be useful in aging and other conditions such as disuse, insulin resistance, or microgravity.

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Section: Discussionmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

Nitric oxide and voluntary exercise together promote quadriceps hypertrophy and increase vascular density in female 18-mo-old mice

Leiter

Upadhaya²,

Anderson

2012

American Journal of Physiology-Cell Physiology

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“…Incorporation of BrdU into activated SC nuclei was detected by immunostaining (Mizunoya et al, 2011;Anderson and Pilipowicz, 2002) with anti-BrdU antibody (Roche Applied Science, Penzberg, Germany, 1:50). cmet+ SCs were detected using anti-c-met primary antibody (Santa Cruz, 1:50).…”

Section: Immunostainingmentioning

confidence: 99%

Satellite cell activation and populations on single muscle-fiber cultures from adult zebrafish (Danio rerio)

Zhang

Anderson

2014

Journal of Experimental Biology

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Satellite cells (SCs), stem cells in skeletal muscle, are mitotically quiescent in adult mammals until activated for growth or regeneration. In mouse muscle, SCs are activated by nitric oxide (NO), hepatocyte growth factor (HGF) and the mechanically induced NO-HGF signaling cascade. Here, the SC population on fibers from the adult, ectothermic zebrafish and SC responsiveness to activating stimuli were assessed using the model system of isolated fibers cultured at 27 and 21°C. SCs were identified by immunostaining for the HGF receptor, c-met, and activation was determined using bromodeoxyuridine uptake in culture or in vivo. In dose-response studies, SC activation was increased by treatment with the NO-donor drug isosorbide dinitrate (1 mmol l −1 ) or HGF (10 ng ml −1 ) to maximum activation at lower concentrations of both than in previous studies of mouse fibers. HGF-induced activation was blocked by anti-c-met antibody, and reduced by culture at 21°C. The effect of cyclical stretch (3 h at 4 cycles per minute) increased activation and was blocked by nitric oxide synthase inhibition and reduced by culture at 21°C. The number of c-met+ SCs per fiber increased rapidly (by 3 h) after stretching. The character of signaling in SC activation on zebrafish fibers, in particular temperature-dependent responses to HGF and stretch, gives new insights into the influence of ectothermy on regulation of muscle growth in teleosts and suggests the use of the single-fiber model system to explore the basis of fiber hyperplasia and the conservation of regulatory pathways between species. KEY WORDS: Stem cells, Ectothermy, Proliferation, c-met, Hepatocyte growth factor INTRODUCTIONSkeletal muscle function in fish is fundamentally important for survival using high-and low-speed swimming (Fauconneau et al., 1995), and the zebrafish [Danio rerio (Hamilton 1822)], an ectothermic teleost, is an important vertebrate model for studying development, physiology and pathology (Lieschke and Currie, 2007). In teleosts, muscle mass [over 90% white fibers (Wakeling and Johnston, 1999)] grows by increases in fiber number and size (Bird and Mabee, 2003;Buckingham and Vincent, 2009). The combination of hyperplasia and hypertrophy is termed indeterminate growth (Fauconneau and Paboeuf, 2001;Rowlerson and Veggetti, 2001;Johnston, 2006), and the growth potential is strongly influenced by temperature (Steinbacher et al., 2011). By comparison, in postnatal mammals, fibers hypertrophy and show accretion of post-mitotic myonuclei, but fibers do not increase in number (Petrella et al., 2008;O'Connor and Pavlath, 2007). Satellite RESEARCH ARTICLEDepartment of Biological Sciences, University of Manitoba, Winnipeg, MB, Canada R3T 2N2. Anderson and Pilipowicz, 2002;Bischoff, 1975;Bischoff, 1986;Bischoff, 1990) and in vivo (Anderson, 2000;Anderson and Wozniak, 2004;Tatsumi and Allen, 2008). Calcium-dependent stretch-activated signals release NO from mechano-sensitive NOS-1μ, which induces HGF release from the extracellular matrix (Tatsumi et al., 2002;Y...

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“…They went on to show that HCT 1026 preserved the number and function of satellite cells and led to a four-fold enhancement in the efficacy of mesoangioblast stem cells to integrate into the muscle, paving the way for a combinational approach to cell therapy in the future [505]. By regulating satellite cell activation, reducing fibre damage, and alleviating some of the detrimental effects of glucocorticoids, the beneficial effects of coadministering NO donor drugs, MyoNovin and isosorbide dinitrate, with prednisolone have recently also demonstrated that NO donors could improve current therapy for DMD [508]. Additional NO donors that specifically target the SM are in early development [509].…”

Section: No/cgmpmentioning

confidence: 99%

Pharmacologically Targeting the Primary Defect and Downstream Pathology in Duchenne Muscular Dystrophy

Fairclough

Perkins²,

Davies³

2012

CGT

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DMD is a devastatingly progressive muscle wasting disorder of childhood that significantly shortens life expectancy. Despite efforts to develop an effective therapy that dates back over a century, clinical interventions are still restricted to management of symptoms rather than a cure. The rationale to develop effective therapies changed in 1986 with the discovery of the dystrophin gene. Since then extensive research into both the molecular basis and pathophysiology of DMD has paved the way not only for development of strategies which aim to correct the primary defect, but also towards the identification of countless therapeutic targets with the potential to alleviate the downstream pathology. In addition to gene and cell-based therapies, which aim to deliver the missing gene and/or protein, an exciting spectrum of pharmacological approaches aimed at modulating therapeutic targets within DMD muscle cells through the use of small drugs are also being developed. This review presents promising pharmacological approaches aimed at targeting the primary defect, including suppression of nonsense mutations and functional compensation by upregulation of the dystrophin homologue, utrophin. Downstream of the primary membrane fragility, inflammation and fibrosis are reduced by blocking NF-κB, TGF-α and TGF-β, and free radical damage has been targeted using antioxidants and dietary/nutritional supplements. There are new hopes that ACE and PDE5 inhibitors can protect against skeletal as well as cardiac pathology, and modulating Ca2+ influx, NO, BMP, protein degradation and the mitochondrial permeability pore hold further promise in tackling the complex pathogenesis of this multifaceted disorder.

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Nitric oxide donors improve prednisone effects on muscular dystrophy in themdxmouse diaphragm

Cited by 26 publications

References 94 publications

Nitric oxide and voluntary exercise together promote quadriceps hypertrophy and increase vascular density in female 18-mo-old mice

Nitric oxide and voluntary exercise together promote quadriceps hypertrophy and increase vascular density in female 18-mo-old mice

Satellite cell activation and populations on single muscle-fiber cultures from adult zebrafish (Danio rerio)

Pharmacologically Targeting the Primary Defect and Downstream Pathology in Duchenne Muscular Dystrophy

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