Insulin-Induced Oxidative Stress Up-Regulates Heme Oxygenase-1 via Diverse Signaling Cascades in the C2 Skeletal Myoblast Cell Line
| العنوان: | Insulin-Induced Oxidative Stress Up-Regulates Heme Oxygenase-1 via Diverse Signaling Cascades in the C2 Skeletal Myoblast Cell Line |
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| المؤلفون: | Isidoros Beis, Catherine Gaitanaki, Dimitris Theofilatos, Ioanna-Katerina Aggeli |
| المصدر: | Endocrinology. 152:1274-1283 |
| بيانات النشر: | The Endocrine Society, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Cell Survival, Myoblasts, Skeletal, medicine.medical_treatment, Blotting, Western, Protoporphyrins, Ascorbic Acid, medicine.disease_cause, Antioxidants, Cell Line, Mice, Endocrinology, medicine, Animals, Insulin, Enzyme Inhibitors, Phosphorylation, Anthracenes, Flavonoids, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Caspase 3, Chemistry, Skeletal Myoblasts, JNK Mitogen-Activated Protein Kinases, NF-kappa B, Catalase, Cell biology, Enzyme Activation, Heme oxygenase, Oxidative Stress, Cell culture, Reactive Oxygen Species, Heme Oxygenase-1, Oxidative stress, Signal Transduction |
| الوصف: | Impaired insulin sensitivity (insulin resistance) is a common denominator in many metabolic disorders, exerting pleiotropic effects on skeletal muscle, liver, and adipose tissue function. Heme oxygenase-1 (HOX-1), the rate-limiting enzyme in heme catabolism, has recently been shown to confer an antidiabetic effect while regulating cellular redox-buffering capacity. Therefore, in the present study, we probed into the mechanisms underlying the effect of insulin on HOX-1 in C2 skeletal myoblasts. Hence, insulin was found to suppress C2 myoblasts viability via stimulation of oxidative stress, with HOX-1 counteracting this action. Insulin induced HOX-1 expression in a time- and dose-dependent manner, an effect attenuated by selective inhibitors of ERK1/2 (PD98059), Src (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d] pyrimidine), and c-Jun terminal kinases 1 and 2 (SP600125) pathways. Furthermore, nuclear factor-κB role in insulin-induced HOX-1 up-regulation was verified, with ERK1/2, Src, and c-Jun terminal kinases 1 and 2 mediating p65-nuclear factor-κB subunit phosphorylation. Overall, our novel findings highlight for the first time the transduction mechanisms mediating HOX-1 induction in insulin-treated C2 myoblasts. This effect was established to be cell type specific because insulin failed to promote HOX-1 expression in HepG2 hepatoma cells. Deciphering the signaling networks involved in insulin-stimulated HOX-1 up-regulation is of prominent significance because it may potentially contribute to elucidation of the mechanisms involved in associated metabolic pathologies. |
| تدمد: | 1945-7170 0013-7227 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b6d29c92269c7d9ad1103831474a7c43 https://doi.org/10.1210/en.2010-1319 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....b6d29c92269c7d9ad1103831474a7c43 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19457170 00137227 |
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