Sphingomyelinase promotes oxidant production and skeletal muscle contractile dysfunction through activation of NADPH oxidase
| العنوان: | Sphingomyelinase promotes oxidant production and skeletal muscle contractile dysfunction through activation of NADPH oxidase |
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| المؤلفون: | James A. Loehr, Reem eAbo-Zahrah, Rituraj ePal, George G. Rodney |
| المصدر: | Frontiers in Physiology, Vol 5 (2015) Frontiers in Physiology |
| بيانات النشر: | Frontiers Media S.A., 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Mitochondrial ROS, Physiology, NADPH Oxidase, Mitochondrion, lcsh:Physiology, Superoxide dismutase, 03 medical and health sciences, 0302 clinical medicine, Nox2, Physiology (medical), medicine, Original Research Article, skeletal muscle, redox signaling, sphingomyelinase, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Gene knockdown, Reactive oxygen species, NADPH oxidase, biology, lcsh:QP1-981, sphingomylenase, Skeletal muscle, ROS, Cell biology, medicine.anatomical_structure, Biochemistry, chemistry, biology.protein, Sphingomyelin, Reactive Oxygen Species, force, 030217 neurology & neurosurgery |
| الوصف: | Elevated concentrations of sphingomyelinase (SMase) have been detected in a variety of diseases. SMase has been shown to increase muscle derived oxidants and decrease skeletal muscle force; however, the sub-cellular site of oxidant production has not been elucidated. Using redox sensitive biosensors targeted to the mitochondria and NADPH oxidase (Nox2), we demonstrate that SMase increased Nox2-dependent ROS and had no effect on mitochondrial ROS in isolated FDB fibers. Pharmacological inhibition and genetic knockdown of Nox2 activity prevented SMase induced ROS production and provided protection against decreased force production in the diaphragm. In contrast, genetic overexpression of superoxide dismutase within the mitochondria did not prevent increased ROS production and offered no protection against decreased diaphragm function in response to SMase. Our study shows that SMase induced ROS production occurs in specific sub-cellular regions of skeletal muscle; however, the increased ROS does not completely account for the decrease in muscle function. |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4df64d38390e5e1cd8c7540596a2f1aaTest http://journal.frontiersin.org/Journal/10.3389/fphys.2014.00530/fullTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4df64d38390e5e1cd8c7540596a2f1aa |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |