Chronic activation of neutral ceramidase protects β-cells against cytokine-induced apoptosis

التفاصيل البيبلوغرافية
العنوان: Chronic activation of neutral ceramidase protects β-cells against cytokine-induced apoptosis
المؤلفون: Cui-ping Liu, Kuanfeng Xu, Xiao-Hong Shan, Qun Zhu, Junfei Jin, Xiaodong Mao, Chao Liu
المصدر: Acta Pharmacologica Sinica. 29:593-599
بيانات النشر: Springer Science and Business Media LLC, 2008.
سنة النشر: 2008
مصطلحات موضوعية: medicine.medical_specialty, Time Factors, medicine.medical_treatment, Apoptosis, Biology, Culture Media, Serum-Free, Gene Expression Regulation, Enzymologic, Cell Line, Flow cytometry, Necrosis, chemistry.chemical_compound, Annexin, Insulin-Secreting Cells, Neutral Ceramidase, Internal medicine, medicine, Animals, Pharmacology (medical), RNA, Messenger, Propidium iodide, Annexin A5, Coloring Agents, Fluorescent Dyes, Pharmacology, medicine.diagnostic_test, General Medicine, Transfection, Molecular biology, Recombinant Proteins, Rats, Enzyme Activation, Endocrinology, Cytokine, chemistry, Cell culture, Cytokines, Fluorescein-5-isothiocyanate, Propidium
الوصف: Aim: To investigate the activity and expression of neutral ceramidase (N-CDase) in the insulin-secreting cell line INS-1 and its role in the cellular response to cytokines. Methods: HPLC, Western blotting, and quantitative real-time PCR were performed to detect the activity and expression of N-CDase in INS-1 cells treated with a cytokine mixture (5 ng/mL interleukin-1β, 10 ng/mL TNF-α, and 50 ng/mL interferon-γ). The expression and activity of N-CDase in the INS-1 cells were specifically inhibited using N-CDase-siRNA transfection. Annexin V-fluorescein-isothiocyanate/propidium iodide flow cytometry was used to assess apoptosis in the INS-1 cells. Results: The INS-1 cells exhibited some basal N-CDase activity, and cytokines induced a time-dependent delay in the activation of N-CDase. As a result, the activation of N-CDase was first detectable at 8 h after stimulation. It peaked at 16 h and remained elevated at 24 h. Cytokines also upregulated the mRNA and protein expression of N-CDase in the INS-1 cells. Furthermore, when N-CDase activity was inhibited by RNA interference, cytokine-induced apoptosis in the INS-1 cells was markedly increased. Conclusion: The N-CDase pathway is active in INS-1 cells, and the chronic activation of N-CDase is involved in the pathological response of β-cells to cytokines, potentially providing protection against cytokine toxicity.
تدمد: 1745-7254
1671-4083
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::909350bea44835006f6faba498b8a844Test
https://doi.org/10.1111/j.1745-7254.2008.00781.xTest
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....909350bea44835006f6faba498b8a844
قاعدة البيانات: OpenAIRE