NOX1 down-regulation attenuated the autophagy and oxidative damage in pig intestinal epithelial cell following transcriptome analysis of transport stress

Gene. 2020 Dec 30:763:145071. doi: 10.1016/j.gene.2020.145071. Epub 2020 Aug 19.

Abstract

The previous study indicated that transport stress resulted in oxidative damage and autophagy/mitophagy elevation, companied by NOX1 over- expression in the jejunal tissues of pigs. However, the transportation-related gene expression profile and NOX1 function in intestine remain to be explicated. In the current study, differentially expressed genes involved in PI3K-Akt and NF-κB pathways, oxidative stress and autophagy process have been identified in pig jejunal tissues after transcriptome analysis following transportation. The physiological functions of NOX1 down-regulation were explored against oxidative damage and excessive autophagy in porcine intestinal epithelial cells (IPEC-1) following NOX1 inhibitor ML171 and H2O2 treatments. NOX1 down-regulation could decrease the content of Malondialdehyde (MDA), Lactic dehydrogenase (LDH) activity and reactive oxygen species (ROS) level, and up-regulate superoxide dismutase (SOD) activity. Furthermore, mitochondrial membrane potential and content were restored, and the expressions of tight junction proteins (Claudin-1 and ZO-1) were also increased. Additionally, NOX1 inhibitior could down-regulate the expression of autophagy-associated proteins (ATG5, LC3, p62), accompanied by activating SIRT1/PGC-1α pathway. NOX1 down-regulation might alleviate oxidative stress-induced mitochondria damage and intestinal mucosal injury via modulating excessive autophagy and SIRT1/PGC-1α signaling pathway. The data will shed light on the molecular mechanism of NOX1 on intestine oxidative damage following pig transportation.

Keywords: Autophagy; NOX1; Oxidative damage; RNA-seq; Transport stress.

MeSH terms

  • Animals
  • Autophagy*
  • Cell Line
  • Enterocytes / metabolism*
  • Female
  • Male
  • Mitochondria / metabolism
  • NADPH Oxidase 1 / genetics
  • NADPH Oxidase 1 / metabolism*
  • Oxidative Stress*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Sirtuins / genetics
  • Sirtuins / metabolism
  • Stress, Psychological / genetics
  • Stress, Psychological / metabolism*
  • Swine
  • Transcriptome*

Substances

  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • NADPH Oxidase 1
  • Sirtuins