کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4932691 1433526 2017 44 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Presenilin 1 mutation decreases both calcium and contractile responses in cerebral arteries
ترجمه فارسی عنوان
جهش پوزسینیلین 1 هر دو واکنش کلسیم و انقباضی در شریانهای مغزی را کاهش می دهد
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
چکیده انگلیسی
Mutations or upregulation in presenilin 1 (PS1) gene are found in familial early-onset Alzheimer's disease or sporadic late-onset Alzheimer's disease, respectively. PS1 has been essentially studied in neurons and its mutation was shown to alter intracellular calcium (Ca2+) signals. Here, we showed that PS1 is expressed in smooth muscle cells (SMCs) of mouse cerebral arteries, and we assessed the effects of the deletion of exon 9 of PS1 (PS1dE9) on Ca2+ signals and contractile responses of vascular SMC. Agonist-induced contraction of cerebral vessels was significantly decreased in PS1dE9 both in vivo and ex vivo. Spontaneous activity of Ca2+ sparks through ryanodine-sensitive channels (RyR) was unchanged, whereas the RyR-mediated Ca2+-release activated by caffeine was shorter in PS1dE9 SMC when compared with control. Moreover, PS1dE9 mutation decreased the caffeine-activated capacitive Ca2+ entry, and inhibitors of SERCA pumps reversed the effects of PS1dE9 on Ca2+ signals. PS1dE9 mutation also leads to the increased expression of SERCA3, phospholamban, and RyR3. These results show that PS1 plays a crucial role in the cerebrovascular system and the vascular reactivity is decreased through altered Ca2+ signals in PS1dE9 mutant mice.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 58, October 2017, Pages 201-212
نویسندگان
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