Induction of xanthine oxidase activity, endoplasmic reticulum stress and caspase activation by sodium metabisulfite in rat liver and their attenuation by Ghrelin
Induction of xanthine oxidase activity, endoplasmic reticulum stress and caspase activation by sodium metabisulfite in rat liver and their attenuation by Ghrelin
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DOI：
10.1016/j.fct.2014.11.021
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发表时间：
2015-02-01
影响因子：
4.3
通讯作者：
Aslan, Mutay
中科院分区：
文献类型：
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作者：
Ercan, Sevim;Kencebay, Ceren;Aslan, Mutay
焦亚硫酸钠在许多食品制备中用作防腐剂，但可氧化成亚硫酸根，引发分子氧化。Ghrelin是一种主要在胃中产生的肽激素，对胃肠道和心血管系统具有抗炎和抗氧化作用。本研究旨在探讨Ghrelin对亚硫酸盐诱导的大鼠外周器官内质网应激和caspase激活的影响。在用焦亚硫酸钠和/或生长素释放肽处理5周的大鼠的肝脏、心脏和肾脏中测定黄嘌呤氧化酶（XO）、黄嘌呤脱氢酶（XDH）酶活性、ER应激标志物[磷酸化PKR样ER激酶（pPERK）; C/EBP同源蛋白（CHOP）]、半胱天冬酶-3、-8、-9活性、核因子κ-B（NF-κ B）水平。焦亚硫酸钠处理显著提高XO活性，诱导GRP 78、CHOP表达，增加肝脏caspase-3、-8和-9活性，但对心脏和肾脏无显著影响。Ghrelin治疗降低XO活性至基线水平，并减弱ER应激和半胱天冬酶激活焦亚硫酸钠治疗大鼠的肝组织。总之，焦亚硫酸钠在肝组织中的代谢增加XO活性，诱导ER应激并引起caspase激活，而Ghrelin处理减弱了这种激活。Ghrelin可能通过调节XO活性发挥其保肝作用。(C)2014爱思唯尔有限公司版权所有。
Sodium metabisulfite is used as a preservative in many food preparations but can oxidize to sulfite radicals initiating molecular oxidation. Ghrelin is a peptide hormone primarily produced in the stomach and has anti-inflammatory and anti-oxidant effects on gastrointestinal and cardiovascular systems. This study was performed to elucidate the effect of ghrelin on sulfite-induced endoplasmic reticulum (ER) stress and caspase activation in rat peripheral organs. Xanthine oxidase (XO), xanthine dehydrogenase (XDH) enzyme activities, ER stress markers [phosphorylated PKR-like ER kinase (pPERK); C/EBP-homologous protein (CHOP)], caspase-3, -8, -9 activities, nuclear factor kappa-B (NF-kappa B) levels were determined in liver, heart and kidney of rats treated with sodium metabisulfite and/or ghrelin for 5 weeks. Sodium metabisulfite treatment significantly elevated XO activity, induced expression of GRP78, CHOP and increased caspase-3, -8 and -9 activities in liver but had no significant effect in heart and kidney. Ghrelin treatment decreased XO activity to baseline levels and attenuated ER stress and caspase activation in liver tissue of sodium metabisulfite treated rats. In conclusion, metabolism of sodium metabisulfite in liver tissue increased XO activity, induced ER stress and caused caspase activation which was attenuated by ghrelin treatment. Ghrelin's hepatoprotective effect could be through modulation of XO activity. (C) 2014 Elsevier Ltd. All rights reserved.