کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2201288 1100009 2010 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Rod photoreceptor cell death is induced by okadaic acid through activation of PKC and L-type voltage-dependent Ca2+ channels and prevented by IGF-1
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Rod photoreceptor cell death is induced by okadaic acid through activation of PKC and L-type voltage-dependent Ca2+ channels and prevented by IGF-1
چکیده انگلیسی
Retinal dystrophies involve extensive photoreceptor apoptosis. Neuroprotective effects of insulin-like growth factor (IGF)-1 have been demonstrated in various tissues, including the retina. The aim of this study was to investigate: (i) the action of IGF-1 upon selective photoreceptor death induced by okadaic acid (OA); and (ii) signaling pathways related to both OA-induced cell death and IGF-1 neuroprotective effect. Retinal explants were incubated with 5 nM OA, a protein phosphatase type 1 and type 2A inhibitor, which induces cell death detected by the identification of pyknotic morphology of photoreceptors immunostained for rhodopsin. OA increased both the number of pyknotic Rho 4D2+ profiles, and Ca2+ influx, measured through the incorporation of 45CaCl2, in a dose- and time-dependent way, while treatment with 10 ng/mL IGF-1 abrogated both effects. Treatment with phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, modulated OA effects, indicating the involvement of PKC. Furthermore, either 10 μM chelerythrine chloride, an inhibitor of PKC, or 10 μM nifedipine, a L-voltage-sensitive Ca2+ channel blocker, inhibited both Ca2+ influx and cell death induced by OA. The data show that okadaic acid induces rod photoreceptor cell death in retinal tissue through activation of PKC and ensuing Ca2+ influx through L-type Ca2+ channels, which is counteracted by a neuroprotective effect of IGF-1.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 57, Issue 2, September 2010, Pages 128-135
نویسندگان
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