Skeletal muscle atrophy is caused by disruption in the homeostatic balance of muscle degeneration and regeneration under various pathophysiological conditions. We have previously reported that iron accumulation induces skeletal muscle atrophy via a ubiquitin ligase–dependent pathway. However, the potential effect of iron accumulation on muscle regeneration remains unclear. To examine the effect of iron accumulation on myogenesis, we used a mouse model with cardiotoxin (CTX)‐induced muscle regeneration in vivo and C2C12 mouse myoblast cells in vitro. In mice with iron overload, the skeletal muscles exhibited increased oxidative stress and decreased expression of satellite cell markers. Following CTX‐induced muscle injury, these mice also displayed delayed muscle regeneration with a decrease in the size of regenerating myofibers, reduced expression of myoblast differentiation markers, and decreased phosphorylation of MAPK signaling pathways. In vitro, iron overload also suppressed the differentiation of C2C12 myoblast cells but the suppression could be reversed by superoxide scavenging using tempol. Excess iron inhibits myogenesis via oxidative stress, leading to an imbalance in skeletal muscle homeostasis. —Ikeda, Y., Satoh, A., Horinouchi, Y., Hamano, H., Watanabe, H., Imao, M., Imanishi, M., Zamami, Y., Takechi, K., Izawa‐Ishizawa, Y., Miyamoto, L., Hirayama, T., Nagasawa, H., Ishizawa, K., Aihara, K.‐I., Tsuchiya, K., Tamaki, T. Iron accumulation causes impaired myogenesis correlated with MAPK signaling pathway inhibition by oxidative stress. FASEB J. 33, 9551–9564 (2019). http://www.fasebj.org
Low serum bilirubin levels are associated with the risk of cardiovascular diseases including peripheral artery disease. Bilirubin is known to exert its property such as antioxidant effect or the enhancement of flow-mediated vasodilation, however, bilirubin action on angiogenesis remains unclear. To investigate the molecular mechanism of bilirubin on angiogenic effect, we first employed C57BL/6J mice with unilateral hindlimb ischemia surgery and divided the mice into two groups (vehicle-treated group and bilirubin-treated group). The analysis of laser speckle blood flow demonstrated the enhancement of blood flow recovery in response to ischemia of mice with bilirubin treatment. The density of capillaries was significantly higher in ischemic-adductor muscles of bilirubin-treated mice. The phosphorylated levels of endothelial nitric oxide synthase (eNOS) and Akt were increased in ischemic skeletal muscles of mice with bilirubin treatment compared with vehicle treatment. In in vitro experiments by using human aortic endothelial cells, bilirubin augmented eNOS and Akt phosphorylation, cell proliferation, cell migration and tube formation. These bilirubin actions on endothelial cell activation were inhibited by LY294002, a phosphatidylinositol 3-kinase inhibitor. In conclusion, bilirubin promotes angiogenesis through endothelial cells activation via Akt-eNOS-dependent manner.
Commercial silicoaluminophosphate molecular sieves (SAPO-34) received alkali treatment with either NaOH (0.2, 0.01, 0.005, or 0.001 M) or NH 4 OH (0.005 M). Treatment with NaOH (0.005 M) increased the water adsorption initial rate of SAPO-34 by 1.4-fold. The alkali treatment introduced Na + adsorption sites into the SAPO-34. The desorption ratio (adsorption at 30˚C and desorption at 100˚C) was 88.2% higher than the original rate (84.3%). On the other hand, after alkali treatment of SAPO-34 using NH 4 OH (0.005 M), calcination resulted in the highest desorption ratio at 91.3%. When combined with calcination, alkali treatment with NH 4 OH introduced H + adsorption sites into SAPO-34, H + adsorption sites feature low levels of interaction with water, which enhanced the desorption ratio, but decreased the initial adsorption rate. These results indicate that treating commercial SAPO-34 with 0.005 M NaOH enhances both the adsorption and desorption behaviors.
Aerosol particles of 99mTc-labeled carbon were prepared by sublimation and introduced in various liquid media. The adsorption of the aquasol and organosol particles were studied for various adsorbing substances and media, with the effect of surface treatment and voltage application. The particles often accumulated at the aqueous-organic interface, and also on the vessel surface in the presence of both aqueous and organic phases.The distribution of the particles was examined by a gamma-camera for different organic phases under various concentrations of electrolytes in the aqueous phase.
Background: Skeletal muscle mass is defined by the homeostatic coordination of muscle degeneration and regeneration under various pathophysiological conditions. We have previously reported that iron accumulation induces skeletal muscle atrophy via the ubiquitin-ligase dependent pathway. However, the actionof iron on muscle myogenesis has remained unclear. In the present study, we investigated the effect of iron on skeletal muscle myogenesis. Methods: We examined muscle regeneration by using cardiotoxin (CTX)-induced muscle injury mice model with or without iron overload in in vivo experiments, and C2C12 mice myoblast cells for in vitro study.Results: In mice with iron overload, the skeletal muscles exhibited an increase in oxidative stress and a decrease in the expression of satellite cells markers such as Pax-7 and MyoD expression. Following CTX-induced muscle injury, mice with iron overload also exhibited delay in muscle regeneration with the reduced size of regenerating myofibres, decreased expression of myogenin and myosin heavy chain, and less phosphorylation of the p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) 1/2. Similarly to the findings in the in vivo experiments, iron treatment also inhibited C2C12 myoblast cells differentiation, and it was ameliorated by a superoxide scavenger drug. Conclusion: Iron accumulation suppresses skeletal muscle myogenesis through inhibiting MAPKs signalling via oxidative stress, causing an imbalance in the skeletal muscle homeostasis.
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