کد مقاله کد نشریه سال انتشار مقاله انگلیسی ترجمه فارسی نسخه تمام متن
5562483 1403426 2018 8 صفحه PDF ندارد دانلود کنید
عنوان انگلیسی مقاله
Eukaryotic translation initiation factor 2 subunit α (eIF2α) inhibitor salubrinal attenuates paraquat-induced human lung epithelial-like A549 cell apoptosis by regulating the PERK-eIF2α signaling pathway
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Eukaryotic translation initiation factor 2 subunit α (eIF2α) inhibitor salubrinal attenuates paraquat-induced human lung epithelial-like A549 cell apoptosis by regulating the PERK-eIF2α signaling pathway
چکیده انگلیسی

•PQ-induced apoptosis in human lung epithelial-like A549 cells was investigated.•PQ-induced A549 cell apoptosis involved the endoplasmic reticulum (ER) stress•Salubrinal attenuated PQ-induced A549 cell apoptosis.•eIF2α played a direct role in salubrinal attenuating PQ-induced A549 cell damage.

Paraquat (PQ), as one of the most widely used herbicides in the world, can cause severe lung damage in humans and animals. This study investigated the underlying molecular mechanism of PQ-induced lung cell damage and the protective role of salubrinal. Human lung epithelial-like A549 cells were treated with PQ for 24 h and were pre-incubated with salubrinal for 2 h, followed by 500 μM of PQ treatment. Silencing eIF2α gene of the A549 cells with siRNA interference method was conducted. Cell morphology, cell viability, apoptosis and caspase-3 activity were assessed by different assays accordingly thereafter. The expression of PERK, p-PERK, ATF6, c-ATF6, IRE1α, p-IRE1α, CHOP, GRP78, p-eIF2α and β-actin was assayed by western blot. The data showed that PQ significantly reduced A549 cell viability, changed cell morphology, induced cell apoptosis and significantly upregulated the levels of GRP78, CHOP, p-PERK, c-ATF6 and p-IRE1α. However, 30 μM salubrinal could attenuate the effects of PQ on damages to A549 cells through upregulating p-eIF2α. In contrast, knocking down eIF2α gene inhabited the effects of salubrinal. These results suggest that PQ-induced A549 cell apoptosis involved endoplasmic reticulum (ER) stress, specially the PERK-eIF2α pathway. Salubrinal attenuated A549 cells from PQ-induced damages through regulation of the PERK-eIF2α signaling.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology in Vitro - Volume 46, February 2018, Pages 58-65
نویسندگان
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