Wu Pei, Liu Yang, Jiang Wei-Dan, Jiang Jun, Zhao Juan, Zhang Yong-An, Zhou Xiao-Qiu, Feng Lin
Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, China.
Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China.
PLoS One. 2017 Jan 18;12(1):e0169888. doi: 10.1371/journal.pone.0169888. eCollection 2017.
The liver and intestine are susceptible to the oxidative damage which could result in several diseases. Choline deficiency induced oxidative damage in rat liver cells. Thus, this study aimed to investigate the potential molecular mechanisms responsible for choline deficiency-induced oxidative damage. Juvenile Jian carp were fed diets differing in choline content [165 (deficient group), 310, 607, 896, 1167 and 1820 mg/kg diet] respectively for 65 days. Oxidative damage, antioxidant enzyme activities and related gene expressions in the hepatopancreas and intestine were measured. Choline deficiency decreased choline and phosphatidylcholine contents, and induced oxidative damage in both organs, as evidenced by increased levels of oxidative-stress markers (malondialdehyde, protein carbonyl and 8-hydroxydeoxyguanosine), coupled with decreased activities of antioxidant enzymes [Copper-zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD), glutathione peroxidase (GPx) and glutathione-S-transferase (GST)]. However, choline deficiency increased glutathione contents in the hepatopancreas and intestine. Furthermore, dietary choline deficiency downregulated mRNA levels of MnSOD, GPx1b, GST-rho, mGST3 and Kelch-like ECH associating protein 1 (Keap1b) in the hepatopancreas, MnSOD, GPx1b, GPx4a, GPx4b, GST-rho, GST-theta, GST-mu, GST-alpha, GST-pi and GST-kappa in the intestine, as well as intestinal Nrf2 protein levels. In contrast, choline deficiency upregulated the mRNA levels of GPx4a, GPx4b, mGST1, mGST2, GST-theta, GST-mu, Keap1a and PKC in the hepatopancreas, mGST3, nuclear factor erythoid 2-related factor 2 (Nrf2) and Keap1a in the intestine, as well as hepatopancreatic Nrf2 protein levels. This study provides new evidence that choline deficiency-induced oxidative damage is associated with changes in the transcription of antioxidant enzyme and Nrf2/Keap1 signaling molecules in the hepatopancreas and intestine. Additionally, this study firstly indicated that choline deficiency induced varied change patterns of different GPx and GST isoforms. Meanwhile, the changes of some GPx and GST isoforms caused by choline deficiency in the intestine were contrary to those in the hepatopancreas.
肝脏和肠道易受氧化损伤，这可能导致多种疾病。胆碱缺乏会诱导大鼠肝细胞发生氧化损伤。因此，本研究旨在探讨胆碱缺乏诱导氧化损伤的潜在分子机制。将幼建鲤分别投喂胆碱含量不同[165（缺乏组）、310、607、896、1167和1820 mg/kg饲料]的饲料65天。测定肝胰腺和肠道中的氧化损伤、抗氧化酶活性及相关基因表达。胆碱缺乏降低了胆碱和磷脂酰胆碱含量，并在两个器官中诱导了氧化损伤，氧化应激标志物（丙二醛、蛋白质羰基和8-羟基脱氧鸟苷）水平升高证明了这一点，同时抗氧化酶[铜锌超氧化物歧化酶（CuZnSOD）、锰超氧化物歧化酶（MnSOD）、谷胱甘肽过氧化物酶（GPx）和谷胱甘肽-S-转移酶（GST）]的活性降低。然而，胆碱缺乏增加了肝胰腺和肠道中的谷胱甘肽含量。此外，饲料胆碱缺乏下调了肝胰腺中MnSOD、GPx1b、GST-rho、mGST3和kelch样ECH相关蛋白1（Keap1b）的mRNA水平，下调了肠道中MnSOD、GPx1b、GPx4a、GPx4b、GST-rho、GST-θ、GST-μ、GST-α、GST-π和GST-κ的mRNA水平以及肠道Nrf2蛋白水平。相反，胆碱缺乏上调了肝胰腺中GPx4a、GPx4b、mGST1、mGST2、GST-θ、GST-μ、Keap1a和PKC的mRNA水平，上调了肠道中mGST3、核因子红细胞2相关因子2（Nrf2）和Keap1a的mRNA水平以及肝胰腺Nrf2蛋白水平。本研究提供了新的证据，表明胆碱缺乏诱导的氧化损伤与肝胰腺和肠道中抗氧化酶及Nrf2/Keap1信号分子转录的变化有关。此外，本研究首次表明胆碱缺乏诱导了不同GPx和GST同工型的不同变化模式。同时，胆碱缺乏在肠道中引起的一些GPx和GST同工型的变化与肝胰腺中的相反。
