3 years ago

Temporal changes in glutathione biosynthesis during the lipopolysaccharide-induced inflammatory response of THP-1 macrophages

Temporal changes in glutathione biosynthesis during the lipopolysaccharide-induced inflammatory response of THP-1 macrophages
How macrophages maintain redox homeostasis in the inflammatory process, in which a large amount of oxidants are produced, remains elusive. In this study, we investigated the temporal changes in the intracellular glutathione (GSH), the master antioxidant, and the expression of glutamate cysteine ligase (GCL), the rate-limiting enzyme for GSH biosynthesis, in the inflammatory response of human macrophages (THP1 cells) to lipopolysaccharide. Intracellular GSH concentration was decreased significantly in the early phase (~6h) of LPS exposure, and then gradually went back to the basal level in the late phase (9–24h). The expression level of the catalytic subunit of GCL (GCLC) followed a similar pattern of change as GSH: its mRNA and protein levels were reduced in the early phase and then back to basal level in the late phase. In contrast, the expression of the modifier subunit of GCL (GCLM) was significantly increased in the phase of LPS exposure. Activation Nrf2, the transcription factor involved in the induction of both GCLC and GCLM, occurred at as early as 3h after LPS exposure; whereas the activation of NF-κB occurred at as early as 30min. Inhibition of NF-κB signaling with SN50 prevented the decrease of GCLC and inhibited Nrf2 activation in response to LPS. These data demonstrate time-dependent changes in the expression of GCL and Nrf2 signaling during the inflammatory response, and that the regulation of GCLC and GCLM might be through different pathways in this process.

Publisher URL: www.sciencedirect.com/science

DOI: S0891584917307918

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.