Arsenic Inhibits Myogenic Differentiation and Muscle Regeneration

Yen, Yuan-Peng; Tsai, Keh–Sung; Chen, Yawen; Huang, Chun-Fa; Yang, Rong‐Sen; Liu, Shing‐Hwa

doi:10.1289/ehp.0901525

Cited by 72 publications

(77 citation statements)

References 53 publications

(57 reference statements)

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“…However, even mouse models of such disorders as DMD or obesity rarely show adipocytes in skeletal muscle. We used a model of muscle fatty degeneration reported in the literature [10,25,26,[54][55][56][57][58][59][60][61]. Injecting glycerol in the muscle destabilizes cell membranes, promoting myofiber damage, significant fat deposits along the muscle, and cell death.…”

Section: Exclusion Of Satellite Cells As a Source Of Myogenic Cells Imentioning

confidence: 99%

Role of Pericytes in Skeletal Muscle Regeneration and Fat Accumulation

Birbrair

Zhang²,

Wang³

et al. 2013

Stem Cells and Development

253

225

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Stem cells ensure tissue regeneration, while overgrowth of adipogenic cells may compromise organ recovery and impair function. In myopathies and muscle atrophy associated with aging, fat accumulation increases dysfunction, and after chronic injury, the process of fatty degeneration, in which muscle is replaced by white adipocytes, further compromises tissue function and environment. Some studies suggest that pericytes may contribute to muscle regeneration as well as fat formation. This work reports the presence of two pericyte subpopulations in the skeletal muscle and characterizes their specific roles. Skeletal muscle from Nestin-GFP/ NG2-DsRed mice show two types of pericytes, Nestin-GFP-/NG2-DsRed + (type-1) and Nestin-GFP + /NG2-DsRed + (type-2), in close proximity to endothelial cells. We also found that both Nestin-GFP-/NG2-DsRed + and Nestin-GFP + /NG2-DsRed + cells colocalize with staining of two pericyte markers, PDGFRb and CD146, but only type-1 pericyte express the adipogenic progenitor marker PDGFRa. Type-2 pericytes participate in muscle regeneration, while type-1 contribute to fat accumulation. Transplantation studies indicate that type-1 pericytes do not form muscle in vivo, but contribute to fat deposition in the skeletal muscle, while type-2 pericytes contribute only to the new muscle formation after injury, but not to the fat accumulation. Our results suggest that type-1 and type-2 pericytes contribute to successful muscle regeneration which results from a balance of myogenic and nonmyogenic cells activation.

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Section: Exclusion Of Satellite Cells As a Source Of Myogenic Cells Imentioning

confidence: 99%

Role of Pericytes in Skeletal Muscle Regeneration and Fat Accumulation

Birbrair

Zhang²,

Wang³

et al. 2013

Stem Cells and Development

253

225

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“…7,8,[16][17][18][19] In skeletal muscle, ATO inhibits myogenic differentiation and muscle regeneration in myoblasts. 20 The myopathy had a delayed course, with progressive aggravation in the 3 months after ATO treatment, dramatic improvement in the next 3 months, and with muscle arsenic content remaining increased during the whole process. This could be related to arsenic metabolism in vivo, as human cells are capable of biotransforming inorganic arsenic compounds, such asATO, into highly toxic species, such as monomethylarsonic acid and dimethylarsinic acid.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial myopathy caused by arsenic trioxide therapy

Echaniz‐Laguna

Benoilid

Vinzio

et al. 2012

Blood

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Arsenic trioxide (ATO) has been successfully used as a treatment for acute promyelocytic leukemia (APL) for more than a decade. Here we report a patient with APL who developed a mitochondrial myopathy after treatment with ATO. Three months after ATO therapy withdrawal, the patient was unable to walk without assistance and skeletal muscle studies showed a myopathy with abundant cytoplasmic lipid droplets, decreased activities of the mitochondrial respiratory chain complexes, multiple mitochondrial DNA (mtDNA) deletions, and increased muscle arsenic content. Six months after ATO treatment was interrupted, the patient recovered normal strength, lipid droplets had decreased in size and number, respiratory chain complex activities were partially restored, but multiple mtDNA deletions and increased muscle arsenic content persisted. ATO IntroductionArsenic trioxide (ATO) has a proven therapeutic efficacy in acute promyelocytic leukemia (APL). [1][2][3][4] In addition, the use of ATO is an appealing option in patients with APL because of its mild long-term toxicity profile compared with chemotherapy, especially with respect to myelosuppression and late complications associated with the use of anthracyclines. 3 However, arsenic is also an environmental carcinogen, with chronic exposure inducing liver injury, peripheral neuropathy, and increased incidence of cancer of the lung, skin, bladder, and liver. 5,6 In mammal cells, arsenic genotoxicity is mainly mediated by mitochondrial damage, including mitochondrial oxidative dysfunction. 7,8 Here we report a patient with APL who developed a delayed, severe, and partially reversible mitochondrial myopathy after being treated with ATO. Case reportA 65-year-old female patient developed fatigue, shortness of breath, and thrombocytopenia. Morphologic examination of bone marrow biopsy demonstrated an abnormal accumulation of promyelocytes, and PCR of bone marrow and peripheral blood cells demonstrated the t(15;17)(q22;q12) translocation and the promyelocytic leukemia/retinoic acid receptor-␣ (PML/RAR␣) fusion gene on chromosome 15. She was diagnosed with APL and treated with all-trans retinoic acid (ATRA), 90 mg/day, for a month. Monitoring for APL relapse using a quantitative PCR test for the PML/RAR␣ t(15;17) transcript was positive, and she was then treated for 4 weeks with ATO, 65 mg weekly, with a total dose of 260 mg. She progressively developed diffuse muscle pain and weakness of all limbs, and ATO treatment was interrupted. In the following 3 months, muscle pain and weakness progressively worsened, and she was admitted with severe weakness of all limbs. Motor examination revealed weakness of proximal upper limbs (grade 4/5 on the Medical Research Council scale) and proximal lower limbs (MRC 2/5), and the patient was unable to walk without assistance. EMG examination showed myopathic changes, and serum creatine kinase levels were mildly increased (220 U/L, N Ͻ 200). Absolute neutrophil count, liver enzyme serum levels, and liver, renal, and thyroid functions were normal, ...

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“…Arsenic may also influence the development of the insulin-responsive glucose transport system [30] by decreasing the phosphorylation of mechanistic target of mTOR and p70, key regulators in this process [42]. Notably, in humans, urinary total arsenic (U-tAs; a biomarker measure of arsenic exposure) is inversely associated with insulin sensitivity levels [43].…”

Section: Mechanisms Of Arsenic-associated Dmmentioning

confidence: 99%

Genetic and epigenetic mechanisms underlying arsenic-associated diabetes mellitus: a perspective of the current evidence

2017

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Chronic exposure to arsenic has been associated with the development of diabetes mellitus (DM), a disease characterized by hyperglycemia resulting from dysregulation of glucose homeostasis. This review summarizes four major mechanisms by which arsenic induces diabetes, namely inhibition of insulin-dependent glucose uptake, pancreatic β-cell damage, pancreatic β-cell dysfunction and stimulation of liver gluconeogenesis that are supported by both in vivo and in vitro studies. Additionally, the role of polymorphic variants associated with arsenic toxicity and disease susceptibility, as well as epigenetic modifications associated with arsenic exposure, are considered in the context of arsenic-associated DM. Taken together, in vitro, in vivo and human genetic/ epigenetic studies support that arsenic has the potential to induce DM phenotypes and impair key pathways involved in the regulation of glucose homeostasis.

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Arsenic Inhibits Myogenic Differentiation and Muscle Regeneration

Cited by 72 publications

References 53 publications

Role of Pericytes in Skeletal Muscle Regeneration and Fat Accumulation

Role of Pericytes in Skeletal Muscle Regeneration and Fat Accumulation

Mitochondrial myopathy caused by arsenic trioxide therapy

Genetic and epigenetic mechanisms underlying arsenic-associated diabetes mellitus: a perspective of the current evidence

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