A Comparative Study on Antioxidant System in Fish Hepatopancreas and Intestine Affected by Choline Deficiency: Different Change Patterns of Varied Antioxidant Enzyme Genes and Nrf2 Signaling Factors

PLoS One. 2017 Jan 18;12(1):e0169888. doi: 10.1371/journal.pone.0169888. eCollection 2017.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Carps / metabolism*
  • Choline / metabolism
  • Choline / pharmacology
  • Choline Deficiency / genetics
  • Choline Deficiency / metabolism*
  • Diet
  • Enzymes / genetics*
  • Enzymes / metabolism
  • Fish Proteins / genetics
  • Fish Proteins / metabolism
  • Gene Expression Regulation, Enzymologic
  • Hepatopancreas / metabolism*
  • Intestinal Mucosa / metabolism*
  • Kelch-Like ECH-Associated Protein 1 / genetics
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Phosphatidylcholines / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction

Substances

  • Antioxidants
  • Enzymes
  • Fish Proteins
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • Phosphatidylcholines
  • Reactive Oxygen Species
  • Choline

Grants and funding

This research was financially supported by the National Basic Research Program of China (973 Program) (2014CB138600), National Science Foundation of China (31502184), Outstanding Talents and Innovative Team of Agricultural Scientific Research (Ministry of Agriculture), the National Department Public Benefit Research Foundation (Agriculture) of China (201003020), the Specialized Research Fund for the Doctoral Program of Higher Education of China (20135103110001), Science and Technology Support Program of Sichuan Province of China (2014NZ0003), Major Scientific and Technological Achievement Transformation Project of Sichuan Province of China (2012NC0007; 2013NC0045), the Demonstration of Major Scientific and Technological Achievement Transformation Project of Sichuan Province of China (2015CC0011), Natural Science Foundation for Young Scientists of Sichuan Province (2014JQ0007). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.