Sulforaphane enriched transcriptome of lung mitochondrial energy metabolism and provided pulmonary injury protection via Nrf2 in mice

Hye Youn Cho, Laura Miller-DeGraff, Terry Blankenship-Paris, Xuting Wang, Douglas A. Bell, Fred Lih, Leesa Deterding, Vijayalakshmi Panduri, Daniel L. Morgan, Masayuki Yamamoto, Anita J. Reddy, Paul Talalay, Steven R. Kleeberger

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Nrf2 is essential to antioxidant response element (ARE)-mediated host defense. Sulforaphane (SFN) is a phytochemical antioxidant known to affect multiple cellular targets including Nrf2-ARE pathway in chemoprevention. However, the role of SFN in non-malignant airway disorders remain unclear. To test if pre-activation of Nrf2-ARE signaling protects lungs from oxidant-induced acute injury, wild-type (Nrf2+/+) and Nrf2-deficient (Nrf2−/−) mice were given SFN orally or as standardized broccoli sprout extract diet (SBE) before hyperoxia or air exposure. Hyperoxia-induced pulmonary injury and oxidation indices were significantly reduced by SFN or SBE in Nrf2+/+ mice but not in Nrf2−/− mice. SFN upregulated a large cluster of basal lung genes that are involved in mitochondrial oxidative phosphorylation, energy metabolism, and cardiovascular protection only in Nrf2+/+ mice. Bioinformatic analysis elucidated ARE-like motifs on these genes. Transcript abundance of the mitochondrial machinery genes remained significantly higher after hyperoxia exposure in SFN-treated Nrf2+/+ mice than in SFN-treated Nrf2−/− mice. Nuclear factor-κB was suggested to be a central molecule in transcriptome networks affected by SFN. Minor improvement of hyperoxia-caused lung histopathology and neutrophilia by SFN in Nrf2−/− mice implies Nrf2-independent or alternate effector mechanisms. In conclusion, SFN is suggested to be as a preventive intervention in a preclinical model of acute lung injury by linking mitochondria and Nrf2. Administration of SFN alleviated acute lung injury-like pathogenesis in a Nrf2-dependent manner. Potential AREs in the SFN-inducible transcriptome for mitochondria bioenergetics provided a new insight into the downstream mechanisms of Nrf2-mediated pulmonary protection.

Original languageEnglish
Pages (from-to)29-44
Number of pages16
JournalToxicology and Applied Pharmacology
Volume364
DOIs
Publication statusPublished - 2019 Feb 1

Keywords

  • Antioxidant response element
  • Broccoli
  • Hyperoxia
  • Lung
  • Microarray

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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