کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4332064 | 1292886 | 2006 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The growth compromised HSV-2 mutant ÎRR prevents kainic acid-induced apoptosis and loss of function in organotypic hippocampal cultures
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
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چکیده انگلیسی
We have previously shown that the HSV-2 anti-apoptotic protein ICP10PK is delivered by the replication incompetent virus mutant ÎRR and prevents kainic acid (KA)-induced epileptiform seizures and neuronal cell loss in the mouse and rat models of temporal lobe epilepsy. The present studies used ÎRR and the ICP10PK deleted virus mutant ÎPK to examine the mechanism of neuroprotection. ÎRR-infected neuronal cells expressed a chimeric protein in which ICP10PK is fused in frame to LacZ (p175) while retaining ICP10PK kinase activity. ÎPK-infected neuronal cells expressed a mutant ICP10 protein that is deleted in the PK domain and is kinase negative (p95). p175 and p95 were expressed in CA3 (86 ± 3%) and CA1 (69 ± 7%) cells from ÎRR or ÎPK-infected organotypic hippocampal cultures (OHC) and 80-85% of the ICP10 positive cells co-stained with antibody to βIII Tubulin (neuronal marker). ÎRR, but not ÎPK, inhibited KA-induced cell death and caspase-3 activation in CA3 neurons, an inhibition seen whether ÎRR was delivered 2 days before or 2 days after KA administration (95% neuroprotection). Neuroprotection was associated with ERK and Akt activation and was abrogated by simultaneous treatment with the MEK (U0126) and PI3-K (LY294002) inhibitors. ÎRR-mediated neuroprotection was associated with increased expression of the anti-apoptotic protein Bag-1 and decreased expression of the pro-apoptotic protein Bad. The surviving neurons retained normal synaptic function potentially related to increased expression of the transcription factor CREB. The data indicate that ÎRR is a promising platform for neuroprotection from excitotoxic injury.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1119, Issue 1, 13 November 2006, Pages 26-39
Journal: Brain Research - Volume 1119, Issue 1, 13 November 2006, Pages 26-39
نویسندگان
Michael D. Gober, Jennifer M. Laing, Scott M. Thompson, Laure Aurelian,