The alteration of calcium homeostasis in adult dystrophic mdx muscle fibers is worsened by a chronic exercise in vivo

Fraysse, Bodvaël; Liantonio, Antonella; Cetrone, Michela; Burdi, Rosa; Pierno, Sabata; Frigeri, Antonio; Pisoni, M. Brambilla; Camerino, Claudia; A, De Luca

doi:10.1016/j.nbd.2004.06.002

Cited by 71 publications

(89 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…29,34 Fluorescent measurements were made using a QuantiCell 900 integrated imaging system (VisiTech International Ltd., Sunderland, UK). Calcium measurements were performed using the membrane-permeant Ca 2ϩ indicator fura 2-acetoxymethyl ester (fura2-AM, Molecular Probes).…”

Section: Fura-2 Microfluorescence Analysesmentioning

confidence: 99%

“…The loading of muscle fibers was performed for 1 hour at room temperature (23°C), in normal physiological solution containing 2.5 mol/L fura2-AM and 0.02% Pluronic-F127 (Molecular Probes). 29,34 Fura-2-loaded muscle fibers were mounted in a glass-bottomed RC-27NE experimental chamber (Warner Instrument Corp., Hamden, USA), modified by the authors. Tendons of the muscle preparations were attached by the means of hair loops, one extremity was clamped to a fixed tube and the other to a mobile one.…”

Section: Fura-2 Microfluorescence Analysesmentioning

confidence: 99%

“…Tendons of the muscle preparations were attached by the means of hair loops, one extremity was clamped to a fixed tube and the other to a mobile one. 29,34 The experimental chamber was placed on the stage of an inverted Eclipse TE300 microscope with a ϫ40 Plan-Fluor objective (Nikon, Japan).…”

Section: Fura-2 Microfluorescence Analysesmentioning

confidence: 99%

“…Then, the sarcomere length was set to ϳ2.4 to 2.5 m as previously described. 29 Pairs of background subtracted images of the fura-2 fluorescence (510 nm) excited at 340 nm and 380 nm were acquired at rest and pixel-to-pixel radiometric images were calculated for each muscle fiber. Autofluorescence, determined in unloaded muscle fibers, was Ͻ2% of total signal and was not subtracted.…”

Section: Fura-2 Microfluorescence Analysesmentioning

confidence: 99%

“…[25][26][27] The CsA treatment has been performed on 4-to 5-weekold mdx mice for 4 to 8 weeks throughout a period of exercise on treadmill, a protocol that worsens the murine pathology by contrasting the spontaneous regeneration and allows to monitor the effectiveness of drug therapies both in vivo and ex vivo. 9,28,29 In vivo we evaluated the ability of CsA to prevent the exercise-induced forelimb muscle strength loss. Creatine kinase level, histological analysis, and markers of fibrosis as well as the level of utrophin expression were determined as indexes of the ability of CsA treatment to contrast muscle damage.…”

mentioning

confidence: 99%

See 4 more Smart Citations

A Multidisciplinary Evaluation of the Effectiveness of Cyclosporine A in Dystrophic Mdx Mice

Nico

Liantonio

et al. 2005

The American Journal of Pathology

Self Cite

114

129

View full text Add to dashboard Cite

Chronic inflammation is a secondary reaction of Duchenne muscular dystrophy and may contribute to disease progression. To examine whether immunosuppressant therapies could benefit dystrophic patients, we analyzed the effects of cyclosporine A (CsA) on a dystrophic mouse model. Mdx mice were treated with 10 mg/kg of CsA for 4 to 8 weeks throughout a period of exercise on treadmill, a protocol that worsens the dystrophic condition. The CsA treatment fully prevented the 60% drop of forelimb strength induced by exercise. A significant amelioration (P < 0.05) was observed in histological profile of CsA-treated gastrocnemius muscle with reductions of nonmuscle area (20%), centronucleated fibers (12%), and degenerating area (50%) compared to untreated exercised mdx mice. Consequently, the percentage of normal fibers increased from 26 to 35% in CsA-treated mice. Decreases in creatine kinase and markers of fibrosis were also observed. By electrophysiological recordings ex vivo, we found that CsA counteracted the decrease in chloride conductance (gCl), a functional index of degeneration in diaphragm and extensor digitorum longus muscle fibers. However, electrophysiology and fura-2 calcium imaging did not show any amelioration of calcium homeostasis in extensor digitorum longus muscle fibers. No significant effect Duchenne muscular dystrophy (DMD) is a fatal genetic disorder for which no definitive cure is available. The X-linked mutation of the dystrophin gene leads to the absence of dystrophin in skeletal muscle fibers, a biochemical defect also observed in the mdx mouse, the murine phenotype of DMD. 1 Dystrophin is a subsarcolemmal protein involved in the link between the contractile machinery and the extracellular matrix. It is generally accepted that the absence of dystrophin weakens the sarcolemma and impairs the transduction of the mechanical signal imposed by the contraction. This leads to a complex and still not fully understood network of interconnected pathogenic events responsible for progressive muscle degeneration; these events involve the increased entrance of calcium, the activation of proteases, and the occurrence of a functional ischemic state. [1][2][3][4] Recent evidence suggests that a chronic inflammatory state is a secondary reaction that strongly contributes to the progression of the pathology. A significant overexpression of inflammatory and immune response genes has been described by microarray in muscle of dystrophic subjects. 5,6 Also, activated helper and cytotoxic T cells have been found to be present in higher number in muscles of dystrophic mdx mice and to promote pathology in this phenotype. 7 According to this view, immunoSupported by Telethon-Italy (to project no. 1150) and the Association Franç ais Contre les Myopathies (as part of postdoctoral fellowships to

show abstract

Section: Fura-2 Microfluorescence Analysesmentioning

confidence: 99%

Section: Fura-2 Microfluorescence Analysesmentioning

confidence: 99%

Section: Fura-2 Microfluorescence Analysesmentioning

confidence: 99%

Section: Fura-2 Microfluorescence Analysesmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

A Multidisciplinary Evaluation of the Effectiveness of Cyclosporine A in Dystrophic Mdx Mice

Nico

Liantonio

et al. 2005

The American Journal of Pathology

Self Cite

114

129

View full text Add to dashboard Cite

show abstract

Growth hormone secretagogues prevent dysregulation of skeletal muscle calcium homeostasis in a rat model of cisplatin‐induced cachexia

Conte

Camerino

Mele

et al. 2017

J cachexia sarcopenia muscle

Self Cite

View full text Add to dashboard Cite

BackgroundCachexia is a wasting condition associated with cancer types and, at the same time, is a serious and dose‐limiting side effect of cancer chemotherapy. Skeletal muscle loss is one of the main characteristics of cachexia that significantly contributes to the functional muscle impairment. Calcium‐dependent signaling pathways are believed to play an important role in skeletal muscle decline observed in cachexia, but whether intracellular calcium homeostasis is affected in this situation remains uncertain. Growth hormone secretagogues (GHS), a family of synthetic agonists of ghrelin receptor (GHS‐R1a), are being developed as a therapeutic option for cancer cachexia syndrome; however, the exact mechanism by which GHS interfere with skeletal muscle is not fully understood.MethodsBy a multidisciplinary approach ranging from cytofluorometry and electrophysiology to gene expression and histology, we characterized the calcium homeostasis in fast‐twitch extensor digitorum longus (EDL) muscle of adult rats with cisplatin‐induced cachexia and established the potential beneficial effects of two GHS (hexarelin and JMV2894) at this level. Additionally, in vivo measures of grip strength and of ultrasonography recordings allowed us to evaluate the functional impact of GHS therapeutic intervention.ResultsCisplatin‐treated EDL muscle fibres were characterized by a ~18% significant reduction of the muscle weight and fibre diameter together with an up‐regulation of atrogin1/Murf‐1 genes and a down‐regulation of Pgc1‐a gene, all indexes of muscle atrophy, and by a two‐fold increase in resting intracellular calcium, [Ca2+]i, compared with control rats. Moreover, the amplitude of the calcium transient induced by caffeine or depolarizing high potassium solution as well as the store‐operated calcium entry were ~50% significantly reduced in cisplatin‐treated rats. Calcium homeostasis dysregulation parallels with changes of functional ex vivo (excitability and resting macroscopic conductance) and in vivo (forelimb force and muscle volume) outcomes in cachectic animals. Administration of hexarelin or JMV2894 markedly reduced the cisplatin‐induced alteration of calcium homeostasis by both common as well as drug‐specific mechanisms of action. This effect correlated with muscle function preservation as well as amelioration of various atrophic indexes, thus supporting the functional impact of GHS activity on calcium homeostasis.ConclusionsOur findings provide a direct evidence that a dysregulation of calcium homeostasis plays a key role in cisplatin‐induced model of cachexia gaining insight into the etiopathogenesis of this form of muscle wasting. Furthermore, our demonstration that GHS administration efficaciously prevents cisplatin‐induced calcium homeostasis alteration contributes to elucidate the mechanism of action through which GHS could potentially ameliorate chemotherapy‐associated cachexia.

show abstract

Adaptive and nonadaptive responses to voluntary wheel running by mdx mice

et al. 2008

View full text Add to dashboard Cite

The purpose of this study was to determine the extent to which hindlimb muscles of mdx mice adapt to a voluntary endurance type of exercise. mdx and C57BL mice engaged in 8 weeks of wheel running or maintained normal cage activities. Beneficial adaptations that occurred in mdx mice included changes in muscle mass, fiber size, and fiber types based on myosin heavy chain (MHC) isoform expression. These adaptations occurred without increases in fiber central nuclei and embryonic MHC expression. An undesirable outcome, however, was that muscle mitochondrial enzyme activities did not improve with exercise in mdx mice as they did in C57BL mice. Cellular remodeling of dystrophic muscle following exercise has not been studied adequately. In this study we found that some, but not all, of the expected adaptations occurred in mdx mouse muscle. We must better understand these (non)adaptations in order to inform individuals with DMD about the benefits of exercise.

show abstract

The alteration of calcium homeostasis in adult dystrophic mdx muscle fibers is worsened by a chronic exercise in vivo

Cited by 71 publications

References 53 publications

A Multidisciplinary Evaluation of the Effectiveness of Cyclosporine A in Dystrophic Mdx Mice

A Multidisciplinary Evaluation of the Effectiveness of Cyclosporine A in Dystrophic Mdx Mice

Growth hormone secretagogues prevent dysregulation of skeletal muscle calcium homeostasis in a rat model of cisplatin‐induced cachexia

Adaptive and nonadaptive responses to voluntary wheel running by mdx mice

Contact Info

Product

Resources

About