کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2582425 1561652 2008 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
La3+ binds to BiP/GRP78 and induces unfolded protein response in HepG2 cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
La3+ binds to BiP/GRP78 and induces unfolded protein response in HepG2 cells
چکیده انگلیسی

The effects of La3+ on the unfolded protein response signaling pathways were investigated in human hepatoblastoma HepG2 cells. Our data showed that La3+ could induce unfolded protein response in HepG2 cells, including a significant increase of BiP/GRP78 level, which is an important ER residential chaperone and an ER stress hallmark, in a concentration and time-dependent manner, UPR transducer IRE1 phosphorylation and splicing activation IRE1 downstream substrate XBP1 mRNA. By using La3+-affinity chromatography, the possible cellular target of La3+ leading to UPR events was shown to be the ER residential chaperone BiP/GRP78. BiP/GRP78 was shown to be a La3+ binding protein and the interaction of La3+ with BiP/GRP78 resulted in dissociation of BiP–IRE1 complexes. La3+ induced dissociation of the BiP/GRP78-IRE1 complex was in a time and concentration manner. The apparent dissociation constant was estimated to be 4 nM. In addition, La3+ was observed to slightly stimulate the production of cellular ROS and cause alteration of intracellular Ca2+, indicating the possible involvement of ROS and Ca2+ alteration in La3+ induced UPR. The present work provides a new perspective for understanding the biological and toxicological effects of La3+.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 176, Issues 2–3, 25 November 2008, Pages 196–203
نویسندگان
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