کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2582878 1561703 2016 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Thapsigargin induces apoptosis when autophagy is inhibited in HepG2 cells and both processes are regulated by ROS-dependent pathway
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Thapsigargin induces apoptosis when autophagy is inhibited in HepG2 cells and both processes are regulated by ROS-dependent pathway
چکیده انگلیسی


• TG can induce both mitochondrial signaling pathway-mediated apoptosis and Beclin-1-dependent autophagy in HepG2 cells.
• ROS play an important role in TG-induced apoptosis and autophagy.
• Restraint of autophagy might be enhanced TG-induced apoptosis through increasing the Bax/Bcl-2 ratio in HepG2 cells.

Thapsigargin (TG), is widely used to induce endoplasmic reticular stress. Treated with TG for a long time, cells suffer the unfolded protein response (UPR) to elude apoptosis, but may activate autophagy. However, the switch between autophagy and apoptosis is unclear. To clarify the key signal for selection of these two protective responses, we studied the correlation of autophagy and apoptosis in HepG2 cells exposed to TG with time. TG induced apoptosis in HepG2 cells was evidenced by typical cell morphological changes and the activation of caspase-12, caspase-9 and caspase-3. Meanwhile, cytochrome c was released following with the dissipation of mitochondrial membrane potential (MMP), and the ratio of Bax/Bcl-2 was increased. TG-induced autophagy was confirmed by the accumulation of MDC, GFP-LC3 staining autophagic vacuoles, and the improved expression of LC3 II and Beclin-1. Additionally, inhibited autophagy via chloroquine (CQ) markedly enhanced the apoptosis induced by TG, which was linked to the Bcl-2 family. Furthermore, TG induced the generation of reactive oxygen species (ROS), and the ROS scavenger effectively suppressed TG-induced apoptosis and autophagy. All these results proved that restraint of autophagy may enhance TG-induced apoptosis through increasing the Bax/Bcl-2 ratio and both processes were regulated by ROS.

Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Environmental Toxicology and Pharmacology - Volume 41, January 2016, Pages 167–179
نویسندگان
, , , , , , , , ,