کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4528831 1625930 2016 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Endoplasmic reticulum stress and dysregulation of calcium homeostasis mediate Cu-induced alteration in hepatic lipid metabolism of javelin goby Synechogobius hasta
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم آبزیان
پیش نمایش صفحه اول مقاله
Endoplasmic reticulum stress and dysregulation of calcium homeostasis mediate Cu-induced alteration in hepatic lipid metabolism of javelin goby Synechogobius hasta
چکیده انگلیسی


• The full-length cDNA sequences of five ERS-related genes were firstly characterized from S. hasta.
• Cu exposure evoked ER stress in liver of S. hasta.
• Ca2+ release from ER was involved in the Cu-induced ER stress change.
• Cu-induced alteration in lipid metabolism was suppressed through the attenuation of ER stress.
• Cu exposure evoked ER stress and SREBP-1c activation in hepatocytes of S. hasta, resulting in dysregulation of hepatic lipid metabolism.

The present study was conducted to investigate the effect of Cu exposure on endoplasmic reticulum (ER) stress and Ca2+ homeostasis, and also explore the underlying mechanism of the ER stress and Ca2+ homeostasis in the Cu-induced change of hepatic lipid metabolism in javelin goby Synechogobius hasta. To this end, four experiments were conducted. In experiment 1, the full-length cDNA sequences of two ER molecular chaperones [glucose-regulated protein 78 (GRP78) and calreticulin (CRT)] and three ER stress sensors [PKR-like ER kinase (PERK), inositol requiring enzyme (IRE)-1α, and activating transcription factor (ATF)-6α] cDNAs were firstly characterized from S. hasta. The predicted amino acid sequences for the S. hasta GRP78, CRT, PERK, IRE-1α and ATF-6α revealed that the proteins contained all of the structural features characteristic in other species. mRNAs of the five genes were expressed in various tissues, but their mRNA levels varied among tissues. In experiment 2, S. hasta were exposed to four waterborne Cu concentrations (control, 19 μg/l, 38 μg/l, and 57 μg/l, respectively) for 60 days. Cu exposure evoked ER stress in liver of S. hasta in a time- and concentration-course change. In experiment 3, specific inhibitors, 2-aminoethyldiphenyl borate (2-APB) and dantrolene, were used to explore whether Ca2+ release from ER was involved in the Cu-induced ER stress change. Dantrolene and 2-APB prevented Cu-induced intracellular Ca2+ elevation, which demonstrated the release of Ca2+ from the ER was mediated by both RyR and IP3R. In experiment 4, a chemical chaperone, 4-phenyl butyric acid (4-PBA), was used to demonstrate whether Cu-induced alteration in lipid metabolism was suppressed through the attenuation of ER stress. Cu exposure evoked ER stress and sterol-regulator element-binding protein-1c (SREBP-1c) activation in hepatocytes of S. hasta, resulting in dysregulation of hepatic lipid metabolism. 4-PBA attenuated the Cu-induced elevation of mRNA expression of ER stress-related genes. For the first time, our study cloned GRP78, CRT, PERK, IRE-1α and ATF-6α genes in S. hasta and demonstrated their differential expression among tissues. Moreover, the study demonstrated the molecular mechanism by which ER stress might underlie the change of lipid metabolism induced by Cu in S. hasta.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Aquatic Toxicology - Volume 175, June 2016, Pages 20–29
نویسندگان
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