کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2572144 1561191 2016 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Sulfur mustard-stimulated proteases and their inhibitors in a cultured normal human epidermal keratinocytes model: A potential approach for anti-vesicant drug development
ترجمه فارسی عنوان
پروتئازهای برانگیخته با خردل گوگرد و مهارکننده های آن ها در یک مدل کراتینوسیت اپیدرمی انسانی عادی کشت شده: روش بالقوه برای توسعه داروهای ضد تاول زا
کلمات کلیدی
سولفور موستارد؛ پروتئاز سرین؛ متالوپروتئیناز؛ مهارکننده پروتئاز؛ Zymography؛ لامینین-5 γ2
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی

Protease stimulation in cultured normal human epidermal keratinocytes (NHEK) due to sulfur mustard (SM) exposure is well documented. However, the specific protease(s) stimulated by SM and the protease substrates remain to be determined. In this study, we observed that SM stimulates several proteases and the epidermal-dermal attachment protein laminin-5 is one of the substrates. We propose that following SM exposure of the skin, laminin-5 degradation causes the detachment of the epidermis from the dermis and, therefore, vesication. We utilized gelatin zymography, Western blotting, immuno-fluorescence staining, and real-time polymerase chain reaction (RT-PCR) analyses to study the SM-stimulated proteases and laminin-5 degradation in NHEK. Two major protease bands (64 kDa and 72 kDa) were observed by zymography in SM-exposed cells. Addition of serine protease inhibitor (aprotinin, 100 μM), or the metalloprotease inhibitor (amastatin, 100 μM) to NHEK cultures prior to SM exposure decreased the SM-stimulated protease bands seen by zymography. These inhibitors completely or partially prevented SM-induced laminin-5 γ2 degradation as seen by Western blotting as well as immuno-fluorescence staining. Our results from Western blotting and RT-PCR studies also indicated that the membrane-type matrix metalloproteinase-1 (MT-MM-1) may be involved in SM-induced skin blistering.To summarize, our results in the NHEK model indicate the following: (a) SM stimulates multiple proteases including serine protease(s), and metalloproteases; (b) SM decreases the level of laminin-5 γ2, which is prevented by either a serine protease inhibitor or a metalloprotease inhibitor and (c) MT-MMP-1 maybe one of the proteases that is involved in skin blistering due to SM exposure.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Reports - Volume 3, 2016, Pages 393–400
نویسندگان
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