کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1991326 1540995 2015 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Progesterone attenuates Aβ25–35-induced neuronal toxicity via JNK inactivation and progesterone receptor membrane component 1-dependent inhibition of mitochondrial apoptotic pathway
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Progesterone attenuates Aβ25–35-induced neuronal toxicity via JNK inactivation and progesterone receptor membrane component 1-dependent inhibition of mitochondrial apoptotic pathway
چکیده انگلیسی


• Progesterone protects neurons against Aβ toxicity by inhibition of mitochondrial apoptotic pathway.
• Progesterone neuroprotection against Aβ toxicity is partly mediated by suppressing JNK activation.
• Progesterone attenuates Aβ25–35-induced neuronal toxicity via progesterone receptor membrane component 1.

Progesterone, which acts as a neurosteroid in nervous system, has been shown to have neuroprotective effects in different experiments in vitro and in vivo. Our previous study demonstrates that progesterone exerts neuroprotections in Alzheimer’s disease-like rats. Present study attempted to evaluate the protective effects of progesterone on Aβ-treated neurons and potential mechanisms involved in neuroprotection. Results showed that treatment with progesterone protected primary cultured rat cortical neurons against Aβ25–35-induced apoptosis. Furthermore, we observed that progesterone alleviated mitochondrial dysfunction by rescuing mitochondrial membrane potential under Aβ challenge. Moreover, progesterone could also attenuate Bax/Bcl-2 proteins ratio upregulation and inhibit the activation of caspase-3 in Aβ-treated neurons. These indicate that progesterone attenuates Aβ25–35-induced neuronal toxicity by inhibiting mitochondria-associated apoptotic pathway. Both classic progesterone receptors (classic PR) and progesterone receptor membrane component 1 (PGRMC1), a special progesterone membrane receptor, are broadly expressed throughout the brain. The protective effect of progesterone was partially abolished by PGRMC1 inhibitor AG205 rather than classic PR antagonist RU486 in this study. Additionally, progesterone protected neurons by inhibiting Aβ-induced activation of JNK, which was an upstream signaling component in Aβ-induced mitochondria-associated apoptotic pathway. But this process was independent of PGRMC1. Taken together, these results suggest that progesterone exerts a protective effect against Aβ25–35-induced insults at least in part by two complementary pathways: (1) progesterone receptor membrane component 1-dependent inhibition of mitochondrial apoptotic pathway, and (2) blocking Aβ-induced JNK activation. The present study provides new insights into the mechanism by which progesterone brings neuroprotection.This article is part of a Special Issue entitled ‘Steroids & Nervous System’.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Journal of Steroid Biochemistry and Molecular Biology - Volume 154, November 2015, Pages 302–311
نویسندگان
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