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Endoplasmic reticulum (ER) stress and cAMP/PKA pathway mediated Zn-induced hepatic lipolysis

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Endoplasmic reticulum (ER) stress and cAMP/PKA pathway mediated Zn-induced hepatic lipolysis. / Song, Yu–Feng; Hogstrand, Christer; Wei, Chuan-Chuan; Wu, Kun; Pan, Ya–Xiong; Luo, Zhi.

In: ENVIRONMENTAL POLLUTION, Vol. 228, 09.2017, p. 256-264.

Research output: Contribution to journalArticle

Harvard

Song, YF, Hogstrand, C, Wei, C-C, Wu, K, Pan, YX & Luo, Z 2017, 'Endoplasmic reticulum (ER) stress and cAMP/PKA pathway mediated Zn-induced hepatic lipolysis', ENVIRONMENTAL POLLUTION, vol. 228, pp. 256-264. https://doi.org/10.1016/j.envpol.2017.05.046

APA

Song, YF., Hogstrand, C., Wei, C-C., Wu, K., Pan, YX., & Luo, Z. (2017). Endoplasmic reticulum (ER) stress and cAMP/PKA pathway mediated Zn-induced hepatic lipolysis. ENVIRONMENTAL POLLUTION, 228, 256-264. https://doi.org/10.1016/j.envpol.2017.05.046

Vancouver

Song YF, Hogstrand C, Wei C-C, Wu K, Pan YX, Luo Z. Endoplasmic reticulum (ER) stress and cAMP/PKA pathway mediated Zn-induced hepatic lipolysis. ENVIRONMENTAL POLLUTION. 2017 Sep;228:256-264. https://doi.org/10.1016/j.envpol.2017.05.046

Author

Song, Yu–Feng ; Hogstrand, Christer ; Wei, Chuan-Chuan ; Wu, Kun ; Pan, Ya–Xiong ; Luo, Zhi. / Endoplasmic reticulum (ER) stress and cAMP/PKA pathway mediated Zn-induced hepatic lipolysis. In: ENVIRONMENTAL POLLUTION. 2017 ; Vol. 228. pp. 256-264.

Bibtex Download

@article{201475d3b8bd47ae9850abd8b50bc141,
title = "Endoplasmic reticulum (ER) stress and cAMP/PKA pathway mediated Zn-induced hepatic lipolysis",
abstract = "The present study was performed to determine the effect of Zn exposure influencing endoplasmic reticulum (ER) stress, explore the underlying molecular mechanism of Zn-induced hepatic lipolysis in a fish species of significance for aquaculture, yellow catfish Pelteobagrus fulvidraco. We found that waterborne Zn exposure evoked ER stress and unfolded protein response (UPR), and activated cAMP/PKA pathway, and up-regulated hepatic lipolysis. The increase in ER stress and lipolysis were associated with activation of cAMP/PKA signaling pathway. Zn also induced an increase in intracellular Ca2+ level, which could be partially prevented by dantrolene (RyR receptor inhibitor) and 2-APB (IP3 receptor inhibitor), demonstrating that the disturbed Ca2+ homeostasis in ER contributed to ER stress and dysregulation of lipolysis. Inhibition of ER stress by PBA attenuated UPR, inhibited the activation of cAMP/PKA pathway and resulted in down-regulation of lipolysis. Inhibition of protein kinase RNA-activated-like ER kinase (PERK) by GSK2656157 and inositol-requiring enzyme (IRE) by STF-083010 differentially influenced Zn-induced changes of lipid metabolism, indicating that PERK and IRE pathways played different regulatory roles in Zn-induced lipolysis. Inhibition of PKA by H89 blocked the Zn-induced activation of cAMP/PKA pathway with a concomitant inhibition of ER stress-mediated lipolysis. Taken together, our findings highlight the importance of the ER stress–cAMP/PKA axis in Zn-induced lipolysis, which provides new insights into Zn toxicology in fish and probably in other vertebrates.",
keywords = "Zn, Lipid metabolism, Endoplasmic reticulum stress, Unfolded protein response, cAMP/PKA pathway",
author = "Yu–Feng Song and Christer Hogstrand and Chuan-Chuan Wei and Kun Wu and Ya–Xiong Pan and Zhi Luo",
year = "2017",
month = "9",
doi = "10.1016/j.envpol.2017.05.046",
language = "English",
volume = "228",
pages = "256--264",
journal = "ENVIRONMENTAL POLLUTION",
issn = "0269-7491",
publisher = "ELSEVIER SCI LTD",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Endoplasmic reticulum (ER) stress and cAMP/PKA pathway mediated Zn-induced hepatic lipolysis

AU - Song, Yu–Feng

AU - Hogstrand, Christer

AU - Wei, Chuan-Chuan

AU - Wu, Kun

AU - Pan, Ya–Xiong

AU - Luo, Zhi

PY - 2017/9

Y1 - 2017/9

N2 - The present study was performed to determine the effect of Zn exposure influencing endoplasmic reticulum (ER) stress, explore the underlying molecular mechanism of Zn-induced hepatic lipolysis in a fish species of significance for aquaculture, yellow catfish Pelteobagrus fulvidraco. We found that waterborne Zn exposure evoked ER stress and unfolded protein response (UPR), and activated cAMP/PKA pathway, and up-regulated hepatic lipolysis. The increase in ER stress and lipolysis were associated with activation of cAMP/PKA signaling pathway. Zn also induced an increase in intracellular Ca2+ level, which could be partially prevented by dantrolene (RyR receptor inhibitor) and 2-APB (IP3 receptor inhibitor), demonstrating that the disturbed Ca2+ homeostasis in ER contributed to ER stress and dysregulation of lipolysis. Inhibition of ER stress by PBA attenuated UPR, inhibited the activation of cAMP/PKA pathway and resulted in down-regulation of lipolysis. Inhibition of protein kinase RNA-activated-like ER kinase (PERK) by GSK2656157 and inositol-requiring enzyme (IRE) by STF-083010 differentially influenced Zn-induced changes of lipid metabolism, indicating that PERK and IRE pathways played different regulatory roles in Zn-induced lipolysis. Inhibition of PKA by H89 blocked the Zn-induced activation of cAMP/PKA pathway with a concomitant inhibition of ER stress-mediated lipolysis. Taken together, our findings highlight the importance of the ER stress–cAMP/PKA axis in Zn-induced lipolysis, which provides new insights into Zn toxicology in fish and probably in other vertebrates.

AB - The present study was performed to determine the effect of Zn exposure influencing endoplasmic reticulum (ER) stress, explore the underlying molecular mechanism of Zn-induced hepatic lipolysis in a fish species of significance for aquaculture, yellow catfish Pelteobagrus fulvidraco. We found that waterborne Zn exposure evoked ER stress and unfolded protein response (UPR), and activated cAMP/PKA pathway, and up-regulated hepatic lipolysis. The increase in ER stress and lipolysis were associated with activation of cAMP/PKA signaling pathway. Zn also induced an increase in intracellular Ca2+ level, which could be partially prevented by dantrolene (RyR receptor inhibitor) and 2-APB (IP3 receptor inhibitor), demonstrating that the disturbed Ca2+ homeostasis in ER contributed to ER stress and dysregulation of lipolysis. Inhibition of ER stress by PBA attenuated UPR, inhibited the activation of cAMP/PKA pathway and resulted in down-regulation of lipolysis. Inhibition of protein kinase RNA-activated-like ER kinase (PERK) by GSK2656157 and inositol-requiring enzyme (IRE) by STF-083010 differentially influenced Zn-induced changes of lipid metabolism, indicating that PERK and IRE pathways played different regulatory roles in Zn-induced lipolysis. Inhibition of PKA by H89 blocked the Zn-induced activation of cAMP/PKA pathway with a concomitant inhibition of ER stress-mediated lipolysis. Taken together, our findings highlight the importance of the ER stress–cAMP/PKA axis in Zn-induced lipolysis, which provides new insights into Zn toxicology in fish and probably in other vertebrates.

KW - Zn

KW - Lipid metabolism

KW - Endoplasmic reticulum stress

KW - Unfolded protein response

KW - cAMP/PKA pathway

UR - http://www.scopus.com/inward/record.url?scp=85019896619&partnerID=8YFLogxK

U2 - 10.1016/j.envpol.2017.05.046

DO - 10.1016/j.envpol.2017.05.046

M3 - Article

VL - 228

SP - 256

EP - 264

JO - ENVIRONMENTAL POLLUTION

JF - ENVIRONMENTAL POLLUTION

SN - 0269-7491

ER -

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