کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
11033915 | 1561724 | 2018 | 31 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Camptothecin enhances c-Myc-mediated endoplasmic reticulum stress and leads to autophagy by activating Ca2+-mediated AMPK
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم کشاورزی و بیولوژیک
دانش تغذیه
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Camptothecin (CPT) from Camptotheca acuminate was discovered for anticancer drugs, which targets topoisomease I. However, whether CPT regulates c-Myc expression has not been understood in endoplasmic reticulum (ER) stress and autophagy. In this study, we found that CPT enhanced c-Myc expression and that the transient knockdown of c-Myc abrogated reactive oxygen species (ROS) generation, which resulted in the accumulation of ER stress-regulating proteins, such as PERK, eIF2α, ATF4, and CHOP. Moreover, the transfection of eIF2α-targeted siRNA attenuated CPT-induced autophagy and decreased the levels of Beclin-1 and Atg7, which indicated that CPT upregulated ER stress-mediated autophagy. In addition, CPT phosphorylated AMPK in response to intracellular Ca2+ release. Ca2+ chelators, ethylene glycol tetraacetic acid and a CaMKII inhibitor, K252a, decreased CPT-induced Beclin-1 and Atg7, and downregulated AMPK phosphorylation, which suggested that CPT-induced Ca2+ release leads to the activation of autophagy through CaMKII-mediated AMPK phosphorylation. CPT also phosphorylated JNK and activated the DNA-binding activity of AP-1; furthermore, knockdown of JNK abolished the expression level of Beclin-1 and Atg7, which implied that the JNK-AP-1 pathway was a potent mediator of CPT-induced autophagy. Our findings indicated that CPT promoted c-Myc-mediated ER stress and ROS generation, which enhances autophagy via the Ca2+-AMPK and JNK-AP-1 pathways.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Food and Chemical Toxicology - Volume 121, November 2018, Pages 648-656
Journal: Food and Chemical Toxicology - Volume 121, November 2018, Pages 648-656
نویسندگان
Rajapaksha Gedara Prasad Tharanga Jayasooriya, Matharage Gayani Dilshara, Wisurumuni Arachchilage Hasitha Maduranga Karunarathne, Ilandarage Menu Neelaka Molagoda, Yung Hyun Choi, Gi-Young Kim,