کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4328595 1614187 2009 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Neuroprotective role of δ-opioid receptors against mitochondrial respiratory chain injury
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Neuroprotective role of δ-opioid receptors against mitochondrial respiratory chain injury
چکیده انگلیسی
It is recognized in recent years that activation of δ-opioid receptor (DOR) elicits neuroprotection against hypoxia and ischemia. However, the underlying mechanisms are not well understood yet. Mitochondrial dysfunction plays a key role in hypoxic neuronal injury, but the effect of DOR activation on neurons with a mitochondrial respiratory chain deficiency is poorly elucidated. In this study we tested the effects of DOR activation and inhibition on cultured cortical neurons after inhibiting mitochondrial respiratory chain with sodium azide (NaN3) in days 8 cultures. Neuronal injury was assessed by lactate dehydrogenase release. Changes in DOR proteins were investigated using an antibody against the N-terminus of the DOR, which recognizes the 60, 48, and 32 kDa proteins. Our main findings are that 1) δ- but not μ-opioid receptor activation reduces NaN3-induced neuronal damage, and this neuroprotective effect is abolished by DOR antagonist (naltrindole, NTI); 2) prolonged DOR inhibition with NTI further increases NaN3-induced neuronal damage; 3) NaN3 treatment down-regulates DOR protein levels in neurons, and the 60 and 32 kDa proteins are particularly sensitive; 4) DADLE, besides activating DOR directly, also reverses the decrease of neuronal DOR protein levels induced by NaN3, which may contribute greatly to its neuroprotective effect; 5) NTI reverses NaN3-induced down-regulation of DOR proteins as well, the effect of NTI amplifying NaN3-induced neuronal damage therefore is probably due to its inhibition on DOR activity only. In conclusion, these data suggest that DOR activation plays an important role in neuroprotection against mitochondrial respiratory chain injury.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1252, 3 February 2009, Pages 183-191
نویسندگان
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