نقش کانال‌های کلسیمی TRPM7 و مسیرPI3K/Akt kinase در اثر حفاظتی فاکتور رشد آندوتلیوم عروقی در مدل سلولی بیماری آلزایمر القاء شده با بتا آمیلوئید

نویسندگان

1 مرکز تحقیقات فیزیولوژی، گروه فیزیولوژی دانشکده پزشکی دانشگاه علوم پزشکی ایران، تهران، ایران

2 گروه روانپزشکی دانشکده پزشکی دانشگاه علوم پزشکی ایران، تهران، ایران

چکیده

مقدمه و هدف: بیماری آلزایمر، یک اختلال نورودژنراتیو پیشرونده است که درآن مرگ نورون‌های قشر مغز و هیپوکامپ هدف اصلی دژنراسیون نورونی هستند. علاوه برفرضیه‌های تجمع بتا آمیلوئید خارج سلولی و تولید کلافه های رشته ای عصبی، یکی از عوامل موثر در پاتولوژی بیماری آلزایمر، آسیب عروقی در افراد سالخورده از جمله اختلال در عملکرد فاکتور رشد آندوتلیال عروقی (Vascular Endothelial Growth Factor  یا VEGF) است. مطالعه حاضر به منظور بررسی اثر پیش درمان مدل سلولی بیماری آلزایمر القا شده توسط Aβ با غلظت‌های مختلف VEGF انجام شد.
 
مواد و روش‌ها: سلول های نوروبلاستمای انسانی (SH-SY5Y) پس از کشت و پاساژ، در گروه‌های کنترل، کنترل پیش تیمار شده با غلظت های 5/0، 1، و 2 نانومولار VEGF، بتا آمیلوئید، بتا آمیلوئید پیش تیمار شده با غلظت های 5/0، 1، و 2 نانومولار VEGF، بتا آمیلوئید پیش تیمار شده با موثرترین غلظت VEGF و آنتاگونیست کانال های TRPM7 (2-APB)، یا مهار کننده Akt بررسی شدند. برای بررسی بقای سلول، از تست سنجش بقای سلولی (MTT assay ) استفاده شد.
 
نتایج: نتایج این مطالعه نشان داد که تیمار با بتا آمیلوئید، بقای سلولی را بطور معنی‌دار کاهش داد (001/0 >P < /span>)، پیش تیمار با VEGF بطور وابسته به غلظت و در حد معنی‌دار موجب افزایش بقای سلولی گردید، و این اثر سودمند در حضور آنتاگونیست کانال‌های TRPM7 یا مهار کننده Akt مشاهده نشد.
 
نتیجه گیری: بطور کلی نتایج این مطالعه نشان داد که VEGF می‌تواند از کاهش بقای سلولی بر اثر بتا آمیلوئید جلوگیری نماید و اثر سودمند آن از طریق کانالهای TRPM7 و مسیر سیگنالینگ PI3K/Akt انجام می‌شود.

کلیدواژه‌ها

عنوان مقاله [English]

Involvement of TRPM7 calcium channels and PI3K/AKT kinase pathway in protective effect of vascular endothelial growth factor in amyloid beta-induced model of Alzheimer’s disease

نویسندگان [English]

  • Jila Mehrabi 1
  • Mehrdad Eftekhar Ardebili 2
  • Mona Amiri 1
  • Tourandokht Baluchnejadmojarad 1
چکیده [English]

Background and Objective: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, in which cortical and hippocampus neurons death is the main target of neurodegeneration. In addition to extracellular beta amyloid accumulation and the production of neural tangles, one of effective factors in the pathology of Alzheimer's disease is vascular injury in the elderly including disturbance in vascular endothelial growth factor (VEGF) function. The present study was conducted to investigate the effect of pre-treatment with different concentrations of VEGF in a cellular model of Aβ-induced Alzheimer's disease.
 
Materials and Methods: After culturing and passaging human neuroblastoma cells (SH-SY5Y), they were evaluated in control, control pretreated with different concentrations of VEGF (0.5, 1 and 2 nM), amyloid beta, amyloid beta with the same concentrations of VEGF, and amyloid beta pretreated with the most effective concentration of VEGF in addition to TRPM7 channels antagonist (2-APB) or AKT inhibitor. For assessment of cell viability, MTT assay was applied.
 
Results: Findings of this study showed that amyloid beta significantly reduces cell viability (p<0.001), VEGF pretreatment significantly increases cell viability in a concentration-dependent manner, and this beneficial effect was not observed in the presence of TRPM7 channels antagonist or AKT inhibitor.
 
Conclusion: It is concluded that VEGF could prevent amyloid beta-induced reduction of cell viability and its beneficial effect is mediated through TRPM7 channels and PI3K/Akt signaling.
 

کلیدواژه‌ها [English]

  • Alzheimer’s disease
  • Amyloid beta
  • Vascular endothelial growth factor
  • TRPM7 channel
  • PI3K/Akt

مراجع

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دانشور پزشکی
دوره 27، شماره 2 - شماره پیاپی 141
141
خرداد و تیر 1398
صفحه 19-26

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