Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8883622 | Aquatic Toxicology | 2018 | 11 Pages |
Abstract
The present study was conducted to explore the underlying mechanism of unfolded protein response (UPR) mediating the Cu-induced changes of hepatic lipogenic metabolism in a low vertebrate, freshwater teleost yellow catfish Pelteobagrus fulvidraco. To this end, three experiments were conducted. In Exp. 1, we cloned the regions of grp78, perk, ire-1α and atf-6α promoters, and found that multiple cAMP-response element binding protein (CREB) binding sites were identified in their promoter regions. Furthermore, these CREB binding sites played crucial role in transcriptional regulation of UPR. In Exp. 2, the involvement of perk, ire-1α and atf-6α in Cu-induced changes of hepatic lipid metabolism was confirmed by specific miRNA. In Exp. 3, the regulatory mechanism of CREB underlying UPR mediating Cu-induced hepatic lipogenic metabolism were investigated. Cu induced UPR via the activation of CREB binding sites in the promoter regions of grp78, perk, ire-1α and atf-6α. In addition, the inhibition of CREB markedly attenuated the Cu-induced up-regulation of hepatic lipogenic metabolism in hepatocytes. This conclusion was further supported by the results from the trial of CREB over-expression. Taken together, the present study indicated that CREB was essential for UPR mediating Cu-induced lipogenic metabolism, supporting a mechanistic link among CREB, UPR and Cu-induced changes of lipid metabolism.
Keywords
stearoyl-CoA desaturaseER stress response elementERSESREBP-1LXRATF6CREBIRE1FASSCDTSSACCGRP78/BiPinositol-requiring enzyme 1acetyl-CoA carboxylasefatty acid synthasetranscription start siteendoplasmic reticulumactivating transcription factor 6cAMP-response element binding protein78-kDa glucose-regulated proteinPERKliver X receptor
Related Topics
Life Sciences
Agricultural and Biological Sciences
Aquatic Science
Authors
Yu-Feng Song, Yi-Huan Xu, Mei-Qing Zhuo, Kun Wu, Zhi Luo,