کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4323832 1613835 2015 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Intracellular translocation of histone deacetylase 5 regulates neuronal cell apoptosis
ترجمه فارسی عنوان
انتقال ویروسی سلول هیستون دیازتیلاز 5 تنظیم آپوپتوز سلول های عصبی را تنظیم می کند
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
چکیده انگلیسی


• Phosphorylation and nuclear export of HDAC5 is involved in NMDA-induced apoptosis of cortical neurons.
• NMDA-induced HDAC5 phosphorylation and nuclear export is dependent of CaMKII activation.
• Nuclear localization of HDAC5 inhibits NMDA-induced apoptosis.
• Inhibition of HDAC5 increases NMDA-induced apoptosis in cortical neurons.

Histone deacetylase 5 (HDAC5) undergoes signal-dependent shuttling between the nucleus and cytoplasm, which is regulated in part by calcium/calmodulin-dependent kinase (CaMK)-mediated phosphorylation. Here, we report that HDAC5 regulates the survival of cortical neurons in pathological conditions. HDAC5 was evenly localized to the nucleus and cytoplasm in cultured cortical neurons. However, in response to 50 μM NMDA conditions that induced neuronal cell apoptosis, nuclear-distributed HDAC5 was rapidly phosphorylated and translocated into cytoplasm of the cultured cortical neurons. Treatment with a CaMKII inhibitor KN93 suppressed HDAC5 phosphorylation and nuclear translocation induced by NMDA, whereas constitutively active CaMKIIα (T286D) stimulated HDAC5 nuclear export. Importantly, we showed that ectopic expression of nuclear-localized HDAC5 in cortical neurons suppressed NMDA-induced apoptosis. Finally, inactivation of HDAC5 by treatment with the class II-specific HDAC inhibitor trichostatin A (TSA) promoted NMDA-induced neuronal cell apoptosis. Altogether, these data identify HDAC5 and its intracellular translocation as key effectors of multiple pathways that regulate neuronal cell apoptosis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1604, 16 April 2015, Pages 15–24
نویسندگان
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