Rice protein reduces DNA damage by activating the p53 pathway and stimulating endogenous antioxidant response in growing and adult rats

J Sci Food Agric. 2019 Oct;99(13):6097-6107. doi: 10.1002/jsfa.9888. Epub 2019 Jul 29.

Abstract

Background: Reactive oxygen species (ROS) can cause DNA damage. Rice protein (RP) inhibits ROS accumulation. However, a link between the reduction of ROS-derived DNA damage and the intake of RP is far from clear. The main objective of this study is to elucidate the effects of RPs on the reduction of DNA damage in growing and adult rats.

Results: An intake of RP for 2 weeks significantly reduced the hepatic accumulation of ROS and 8-hydroxydeoxyguanosine (8-OHdG) in growing and adult rats, whereas the hepatic p53 content was markedly increased by RPs. After 2 weeks' feeding, the mRNA levels and protein expressions of p53, ataxia-telangiectasia mutated (ATM), and Checkpoint kinase 2 (Chk2) were up-regulated by RPs, whereas Murine Double Minute 2 (MDM2) expressions were markedly inhibited by RPs, resulting in more p53 being translocated into the nucleus. Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) was activated by RP by reducing Kelch-like ECH-associated protein 1 (Keap1), resulting in the up-regulation of antioxidant expressions of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in RP groups.

Conclusion: Rice protein can exert an endogenous antioxidant activity to reduce ROS-derived DNA damage by activating the Nrf2-Keap1 pathway. This study suggests that the activation of the ATM-Chk2-p53 pathway might be one of the mechanisms exerted by RP for reducing DNA damage in growing and adult rats. © 2019 Society of Chemical Industry.

Keywords: DNA damage; Rice protein; antioxidant response; growing and adult rats; p53.

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Catalase / genetics
  • Catalase / metabolism
  • Checkpoint Kinase 2 / genetics
  • Checkpoint Kinase 2 / metabolism
  • DNA Damage*
  • Glutathione / metabolism
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Kelch-Like ECH-Associated Protein 1 / genetics
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • Liver / metabolism
  • Male
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Oryza / metabolism*
  • Oxidative Stress
  • Plant Proteins / metabolism*
  • Proto-Oncogene Proteins c-mdm2 / genetics
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • Rats
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Antioxidants
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • Plant Proteins
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Mdm2 protein, rat
  • Proto-Oncogene Proteins c-mdm2
  • Checkpoint Kinase 2
  • Chek2 protein, rat
  • Glutathione