Low-Dose Benzo(a)pyrene and Its Epoxide Metabolite Inhibit Myogenic Differentiation in Human Skeletal Muscle-Derived Progenitor Cells

Chiu, Chen‐Yuan; Yen, Yuan-Peng; Tsai, Keh–Sung; Yang, Rong‐Sen; Liu, Shing‐Hwa

doi:10.1093/toxsci/kfu003

Cited by 17 publications

(13 citation statements)

References 45 publications

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“…have shown that arsenic exposure effectively retards myogenesis via the inhibition of Akt signalling . Down‐regulation of Akt signalling was also demonstrated to be involved in benzo(a)pyrene‐induced myogenic differentiation inhibition . In the present study, we found that acrolein dose dependently inhibited Akt phosphorylation during myogenic differentiation.…”

Section: Discussionsupporting

confidence: 68%

“…We further found that acrolein (0.125–1 μM) suppressed the protein expression of MHC and myogenin in differentiated C2C12 myoblasts ( Figure A). Acrolein also reduced the creatine kinase activity, a marker of myoblast myogenesis, in a dose‐dependent manner ( Figure B). These results revealed that acrolein was capable of inhibiting myoblast differentiation and myotube formation in cultured C2C12 myoblasts.…”

Section: Resultsmentioning

confidence: 85%

“…The extraction of cellular protein and western blot analysis were performed as previously described . Cell lysates were separated on 8% or 10% sodium dodecyl sulfate polyacrylamide gel electrophoresis and then electrotransferred onto polyvinylidene difluoride membrane.…”

Section: Methodsmentioning

confidence: 99%

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Adverse effects of acrolein, a ubiquitous environmental toxicant, on muscle regeneration and mass

Chen

Wang

Chan

et al. 2018

J cachexia sarcopenia muscle

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Background Acrolein is an extremely electrophilic aldehyde. Increased urinary acrolein adducts have been found in type 2 diabetic patients and people with a smoking habit. The increased blood acrolein was shown in patients who received the cancer drug cyclophosphamide. Both diabetes and smoking are risk factors for skeletal muscle wasting or atrophy. Acrolein has been found to induce myotube atrophy in vitro . The in vitro and in vivo effects and mechanisms of acrolein on myogenesis and the in vivo effect of acrolein on muscle wasting still remain unclear. Methods C2C12 myoblasts were used to assess the effects of low‐dose acrolein (0.125–1 μM) on myogenesis in vitro . Mice were exposed daily to acrolein in distilled water by oral administration (2.5 and 5 mg/kg) for 4 weeks with or without glycerol‐induced muscle injury to investigate the effects of acrolein on muscle wasting and regeneration. Results Non‐cytotoxic‐concentration acrolein dose dependently inhibited myogenic differentiation in myoblasts (myotube formation inhibition: 0.5 and 1 μM, 66.25% and 46.25% control, respectively, n = 4, P < 0.05). The protein expression for myogenesis‐related signalling molecules (myogenin and phosphorylated Akt: 0.5 and 1 μM, 85.15% and 51.52% control and 62.63% and 56.57% control, respectively, n = 4, P < 0.05) and myosin heavy chain (MHC: 0.5 and 1 μM, 63.64% and 52.53% control, n = 4, P < 0.05) were decreased in acrolein‐treated myoblasts. Over‐expression of the constitutively active form of Akt in myoblasts during differentiation prevented the inhibitory effects of acrolein (1 μM) on myogenesis (MHC and myogenin protein expression: acrolein with or without constitutively active Akt, 64.65% and 105.21% control and 69.14% and 102.02% control, respectively, n = 5, P < 0.05). Oral administration of acrolein for 4 weeks reduced muscle weights (5 mg/kg/day: 65.52% control, n = 6, P < 0.05) and cross‐sectional area of myofibers in soleus muscles (5 mg/kg/day: 79.92% control, n = 6, P < 0.05) with an up‐regulation of atrogin‐1 and a down‐regulation of phosphorylated Akt protein expressions. Acrolein retarded soleus muscle regeneration in a glycerol‐induced muscle regeneration mouse model (5 mg/kg/day: 49.29% control, n = 4, P < 0.05). Acrolein exposure reduced muscle endurance during rotarod fatigue performance in mice with or without glycerol‐induced muscle injury (5 mg/kg/day without glycerol: 30.43% control, n ...

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Section: Discussionsupporting

confidence: 68%

Section: Resultsmentioning

confidence: 85%

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Adverse effects of acrolein, a ubiquitous environmental toxicant, on muscle regeneration and mass

Chen

Wang

Chan

et al. 2018

J cachexia sarcopenia muscle

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“…Widrick et al . have also shown that ALN, at a dosage shown to improve bone loss, did not affect the skeletal muscle function in ovariectomized rats . Moreover, the results from Shiomi et al .…”

Section: Discussionmentioning

confidence: 92%

“…Moreover, muscle fibre atrophy has been reported to be an obvious histological phenomenon of people with sarcopenia and muscle wasting diseases . Muscle growth retardation related to low birth weight of foetus has also been shown to be associated with myogenic inhibition by several risk factors, including polycyclic aromatic hydrocarbons and arsenic . An appropriate remedy for skeletal muscle atrophy and dysfunction needs to be discovered.…”

Section: Introductionmentioning

confidence: 99%

Preventing muscle wasting by osteoporosis drug alendronate in vitro and in myopathy models via sirtuin‐3 down‐regulation

Chiu

Yang

et al. 2018

J cachexia sarcopenia muscle

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Background A global consensus on the loss of skeletal muscle mass and function in humans refers as sarcopenia and cachexia including diabetes, obesity, renal failure, and osteoporosis. Despite a current improvement of sarcopenia or cachexia with exercise training and supportive therapies, alternative and specific managements are needed to discover for whom are unable or unwilling to embark on these treatments. Alendronate is a widely used drug for osteoporosis in the elderly and postmenopausal women. Osteopenic menopausal women with 6 months of alendronate therapy have been observed to improve not only lumbar bone mineral density but also handgrip strength. However, the effect and mechanism of alendronate on muscle strength still remain unclear. Here, we investigated the therapeutic potential and the molecular mechanism of alendronate on the loss of muscle mass and strength in vitro and in vivo. Methods Mouse myoblasts and primary human skeletal muscle-derived progenitor cells were used to assess the effects of low-dose alendronate (0.1-1 μM) combined with or without dexamethasone on myotube hypertrophy and myogenic differentiation. Moreover, we also evaluated the effects of low-dose alendronate (0.5 and 1 mg/kg) by oral administration on the limb muscle function and morphology of mice with denervation-induced muscle atrophy and glycerol-induced muscle injury. Results Alendronate inhibited dexamethasone-induced myotube atrophy and myogenic differentiation inhibition in mouse myoblasts and primary human skeletal muscle-derived progenitor cells. Alendronate significantly abrogated dexamethasone-up-regulated sirtuin-3 (SIRT3), but not SIRT1, protein expression in myotubes. Both SIRT3 inhibitor AKG7 and SIRT3-siRNA transfection could also reverse dexamethasone-up-regulated atrogin-1 and SIRT3 protein expressions. Animal studies showed that low-dose alendronate by oral administration ameliorated the muscular malfunction in mouse models of denervation-induced muscle atrophy and glycerol-induced muscle injury with a negative regulation of SIRT3 expression. Conclusions The putative mechanism by which muscle atrophy was improved with alendronate might be through the SIRT3 down-regulation. These findings suggest that alendronate can be a promising therapeutic strategy for management of muscle wasting-related diseases and sarcopenia.

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Transplantation of human skeletal muscle-derived progenitor cells ameliorates knee osteoarthritis in streptozotocin-induced diabetic mice

et al. 2017

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The epidemiological and experimental evidence suggests that diabetes can be an independent risk factor for osteoarthritis. The osteoarthritis-like cartilage damage has been shown in streptozotocin-induced diabetic mice. The therapeutic effects of human skeletal muscle-derived progenitor cells (HSMPCs) on diabetic osteoarthritis still remain unclear. Here, we investigated the therapeutic potential of HSMPCs on diabetic knee osteoarthritis. The in vitro chondrogenic ability of HSMPCs was determined by pellet culture assay. Male mice were used to develop the model of streptozotocin-induced type 1 diabetes and its related osteoarthritis. HSMPCs were injected intra-articularly to rescue osteoarthritis. Protein expressions of advanced glycation end-products, cyclooxygenase-2, and type-2 collagen in tissues were determined by immunohistochemistry. The pellet culture assay showed that HSMPCs cultured in differentiation medium for chondrogenesis significantly produced larger pellets with an overproduction of extracellular matrix than in growth medium. In in vivo experiments, intra-articular injection of HSMPCs for 4 weeks significantly prevented the progression of degenerative changes in the cartilage of streptozotocin-induced diabetic mice, including an obvious increase of total articular cartilage thickness and a decrease of fibrous cartilage thickness. HSMPCs transplantation also exerted the decline in advanced glycation end-products and cyclooxygenase-2 protein expression, but increased the type-2 collagen protein expression in streptozotocin-induced osteoarthritic cartilages. Moreover, HSMPCs transplantation also inhibited the increased serum interleukin-6 and matrix metalloproteinase-3 levels in diabetic mice. These results demonstrated for the first time that HSMPCs transplantation ameliorates cartilage degeneration in diabetes-related osteoarthritis mice. These findings suggest that HSMPCs transplantation may apply as a potential therapeutic use of diabetes-related osteoarthritis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1886-1893, 2017.

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Low-Dose Benzo(a)pyrene and Its Epoxide Metabolite Inhibit Myogenic Differentiation in Human Skeletal Muscle-Derived Progenitor Cells

Cited by 17 publications

References 45 publications

Adverse effects of acrolein, a ubiquitous environmental toxicant, on muscle regeneration and mass

Adverse effects of acrolein, a ubiquitous environmental toxicant, on muscle regeneration and mass

Preventing muscle wasting by osteoporosis drug alendronate in vitro and in myopathy models via sirtuin‐3 down‐regulation

Transplantation of human skeletal muscle-derived progenitor cells ameliorates knee osteoarthritis in streptozotocin-induced diabetic mice

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