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The Protective Effect of Insulin on Rat Cortical Neurons in Oxidative Stress and Its Dependence on the Modulation of Akt, GSK-3beta, ERK1/2, and AMPK Activities

التفاصيل البيبلوغرافية
العنوان: The Protective Effect of Insulin on Rat Cortical Neurons in Oxidative Stress and Its Dependence on the Modulation of Akt, GSK-3beta, ERK1/2, and AMPK Activities
المؤلفون: Irina O. Zakharova, Tatiana V. Sokolova, Liubov V. Bayunova, Inna I. Zorina, Maria P. Rychkova, Alexander O. Shpakov, Natalia F. Avrova
المصدر: International Journal of Molecular Sciences, Vol 20, Iss 15, p 3702 (2019)
بيانات النشر: MDPI AG, 2019.
سنة النشر: 2019
المجموعة: LCC:Biology (General)
LCC:Chemistry
مصطلحات موضوعية: insulin, cortical neurons, oxidative stress, protection, protein kinases, Bax/Bcl-2 ratio, mitochondrial membrane potential, Biology (General), QH301-705.5, Chemistry, QD1-999
الوصف: Insulin is a promising drug for the treatment of diseases associated with brain damage. However, the mechanism of its neuroprotective action is far from being understood. Our aim was to study the insulin-induced protection of cortical neurons in oxidative stress and its mechanism. Immunoblotting, flow cytometry, colorimetric, and fluorometric techniques were used. The insulin neuroprotection was shown to depend on insulin concentration in the nanomolar range. Insulin decreased the reactive oxygen species formation in neurons. The insulin-induced modulation of various protein kinase activities was studied at eight time-points after neuronal exposure to prooxidant (hydrogen peroxide). In prooxidant-exposed neurons, insulin increased the phosphorylation of GSK-3beta at Ser9 (thus inactivating it), which resulted from Akt activation. Insulin activated ERK1/2 in neurons 5−30 min after cell exposure to prooxidant. Hydrogen peroxide markedly activated AMPK, while it was for the first time shown that insulin inhibited it in neurons at periods of the most pronounced activation by prooxidant. Insulin normalized Bax/Bcl-2 ratio and mitochondrial membrane potential in neurons in oxidative stress. The inhibitors of the PI3K/Akt and MEK1/2/ERK1/2 signaling pathways and the AMPK activator reduced the neuroprotective effect of insulin. Thus, the protective action of insulin on cortical neurons in oxidative stress appear to be realized to a large extent through activation of Akt and ERK1/2, GSK-3beta inactivation, and inhibition of AMPK activity increased by neuronal exposure to prooxidant.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1422-0067
Relation: https://www.mdpi.com/1422-0067/20/15/3702; https://doaj.org/toc/1422-0067
DOI: 10.3390/ijms20153702
URL الوصول: https://doaj.org/article/e67e22170bda43c2b2dd537f6d42e27c
رقم الأكسشن: edsdoj.67e22170bda43c2b2dd537f6d42e27c
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:14220067
DOI:10.3390/ijms20153702