Melanocytes — A novel tool to study mitochondrial dysfunction in Duchenne muscular dystrophy

Pellegrini, Camilla; Zulian, Alessandra; Gualandi, Francesca; Manzati, Elisa; Merlini, Luca; Michelini, M.E.; Benassi, Luisa; Ferlini, Alessandra; Maraldi, Nadir M.; Bernardi, Paolo; Sabatelli, Patrizia

doi:10.1016/j.bbabio.2012.06.417

Cited by 6 publications

(6 citation statements)

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“…Neonatal foreskin tissue was processed as previously described (Pellegrini et al., ; Roberts et al., ). Following incubation with Dispase II, the epidermal sheets were removed and washed twice in PBS.…”

Section: Methodsmentioning

confidence: 99%

Molecular analysis of common polymorphisms within the human Tyrosinase locus and genetic association with pigmentation traits

Jagirdar

Smit

Ainger

et al. 2014

Pigment Cell Melanoma Res

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Summary We have compared the melanogenic activities of cultured melanocytes carrying two common TYR alleles as homozygous 192S-402R wildtype, heterozygous and homozygous variant. This includes assays of TYR protein, DOPAoxidase activity, glycosylation and temperature sensitivity of protein and DOPAoxidase levels. Homozygous wildtype strains on average had higher levels of TYR protein and enzyme activity than other genotypes. Homozygous 402Q/Q melanocytes produced significantly less TYR protein, displayed altered trafficking and glycosylation, with reduced DOPAoxidase. However, near wildtype TYR activity levels could be recovered at lower growth temperature. In a sample population from Southeast Queensland these two polymorphisms were present on four TYR haplotypes, designated as WT 192S-402R, 192Y-402R, 192S-402Q with a double variant 192Y-402Q of low frequency at 1.9%. Based on cell culture findings and haplotype associations, we have used an additive model to assess the penetrance of the ten possible TYR genotypes derived from the combination of these haplotypes.

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Section: Methodsmentioning

confidence: 99%

Molecular analysis of common polymorphisms within the human Tyrosinase locus and genetic association with pigmentation traits

Jagirdar

Smit

Ainger

et al. 2014

Pigment Cell Melanoma Res

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“…Mutations in the 5′ end of the gene affect only the three longest isoforms, Dp427c, Dp427m, and Dp427p, expressed in cortical neurons, skeletal, and cardiac muscles, and Purkinje cells of the cerebellum, respectively . Mutations further downstream, however, affect increasingly more isoforms . Mutations between exon 31 and 44 will also affect Dp260 expression (found mostly in the retina) while mutations between exons 45 and 62 will additionally disrupt Dp140 (found in the brain, retina, kidneys) and Dp116 (found in Schwann cells of the peripheral nerves).…”

Section: Introductionmentioning

confidence: 99%

Neurodevelopmental, behavioral, and emotional symptoms common in Duchenne muscular dystrophy

et al. 2020

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Introduction We studied neurodevelopmental and behavioral/emotional symptoms in patients with Duchenne muscular dystrophy (DMD). Methods Retrospective case series of neurodevelopmental and behavioral/emotional symptoms obtained through review of systems of 700 DMD patients in relation to dystrophin gene mutations. Results The most common symptoms encountered were emotional/behavioral dysregulation (38.7%), inattention/hyperactive features (31.4%), obsessive and compulsive features (25.0%), and language/speech delays (24.4%). Most patients (72.7%) had at least one symptom. Patients with mutations near the 3′ end of the dystrophin gene were at higher risk for developing inattention/hyperactive features, language/speech delays, and global intellectual delays. Those with mutations between exon 31 and 79 had higher risk of clustering of symptoms when compared with those upstream of exon 30. Discussion Neurodevelopmental, emotional, and behavioral symptoms are common comorbidities in DMD. There is higher prevalence of inattention/hyperactive features, language/speech delays, and global intellectual delays in genotypes affecting the 3′ end of the dystrophin gene.

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“…Many of these mutations cause cell membrane disruption , which may trigger cytoplasmic and/or mitochondrial calcium overload . Calcium overload can induce mitochondrial swelling and organelle dysfunction, which can lead to high levels of reactive oxygen species (ROS) and thus tissue oxidative stress (OS) .…”

Section: Introductionmentioning

confidence: 99%

(–)‐Epicatechin improves mitochondrial‐related protein levels and ameliorates oxidative stress in dystrophic δ‐sarcoglycan null mouse striated muscle

et al. 2014

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Muscular dystrophies (MD) are a group of heterogeneous genetic disorders characterized by progressive striated muscle wasting and degeneration. Although the genetic basis for many of these disorders has been identified, the exact mechanism for disease pathogenesis remains unclear. The presence of oxidative stress (OS) is known to contribute to the pathophysiology and severity of the MD. Mitochondrial dysfunction is observed in MD and likely represents an important determinant of increased OS. Experimental antioxidant therapies have been implemented with the aim of protecting against disease progression, but results from clinical trials have been disappointing. In this study, we explored the capacity of the cacao flavonoid (−)-epicatechin (Epi) to mitigate OS by acting as a positive regulator of mitochondrial structure/function endpoints and redox balance control systems in skeletal and cardiac muscles of dystrophic, δ-sarcoglycan (δ-SG) null mice. Wild type or δ-SG null 2.5 month old male mice were treated via oral gavage with either water (control animals) or Epi (1 mg/kg, twice/day) for 2 weeks. Results evidence a significant normalization of total protein carbonylation, recovery of reduced/oxidized glutathione (GSH/GSSG ratio) and enhanced superoxide dismutase 2, catalase and citrate synthase activities with Epi treatment. These effects were accompanied by increases in protein levels for thiolredoxin, glutathione peroxidase, superoxide dismutase 2, catalase and mitochondrial endpoints. Furthermore, we evidence decreases in heart and skeletal muscle fibrosis, accompanied with an improvement in skeletal muscle function with treatment. These results warrant the further investigation of Epi as a potential therapeutic agent to mitigate MD associated muscle degeneration.

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Melanocytes — A novel tool to study mitochondrial dysfunction in Duchenne muscular dystrophy

Cited by 6 publications

References 0 publications

Molecular analysis of common polymorphisms within the human Tyrosinase locus and genetic association with pigmentation traits

Molecular analysis of common polymorphisms within the human Tyrosinase locus and genetic association with pigmentation traits

Neurodevelopmental, behavioral, and emotional symptoms common in Duchenne muscular dystrophy

(–)‐Epicatechin improves mitochondrial‐related protein levels and ameliorates oxidative stress in dystrophic δ‐sarcoglycan null mouse striated muscle

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