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Tert-butylhydroquinone protects PC12 cells against ferrous sulfate-induced oxidative and inflammatory injury via the Nrf2/ARE pathway.

Abstract
Increasing evidence had proved the critical role of iron in the pathogenesis of numerous neurodegenerative diseases because of its capacity to promote the formation of reactive oxygen species (ROS). Tert-butylhydroquinone (tBHQ) was a metabolite of butylated hydroxyanisole, a widely used food antioxidant. This study was aimed to investigate the protective effects of tBHQ on a cellular model of neurodegenerative disease, which was established in PC12 cells by exposure to ferrous sulfate (FS), and elucidate the potential protective mechanisms. The results showed that FS exposure increased lactate dehydrogenase (LDH) release and cell apoptosis in PC12 cells, accompanied by significant increases in the bax/bcl-2 ratio, cytochrome c release, and caspase-3 cleavage. It also enhanced the ROS production, malondialdehyde (MDA) content (lipid peroxidation), γ-H2A.X formation (DNA damage), and promoted nuclear factor kappa B (NF-κB) activation and expressions of cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). tBHQ pretreatment alleviated FS-induced LDH release, cell apoptosis, oxidative stress and inflammatory response by promoting Nrf2 nuclear translocation and the protein levels of Nrf2 downstream target genes heme oxygenase-1 (Hmox-1), nicotinamide adenine dinucleotide phosphate (NADPH): quinone oxidoreductase-1 (Nqo1) and glutathione peroxidase-1 (Gpx1). tBHQ alleviated the FS-induced LDH release in control siRNA-treated PC12 cells, but failed to alleviate FS-induced LDH release in Nrf2 siRNA-treated cells. These findings suggested that pretreatment with tBHQ protected PC12 cells from FS-induced oxidative and inflammatory injury via the Nrf2/ARE pathway. tBHQ was promising as a potential therapeutic agent for neurodegenerative diseases induced by iron toxicity and should be encouraged for further research.
AuthorsWenzhe Xu, Feng Li, Zhenkuan Xu, Bin Sun, Jingwei Cao, Yuguang Liu
JournalChemico-biological interactions (Chem Biol Interact) Vol. 273 Pg. 28-36 (Aug 01 2017) ISSN: 1872-7786 [Electronic] Ireland
PMID28583816 (Publication Type: Journal Article)
CopyrightCopyright © 2017 Elsevier B.V. All rights reserved.
Chemical References
  • Ferrous Compounds
  • Hydroquinones
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Protective Agents
  • ferrous sulfate
  • 2-tert-butylhydroquinone
Topics
  • Animals
  • Antioxidant Response Elements (genetics)
  • Ferrous Compounds (pharmacology)
  • Hydroquinones (pharmacology)
  • Inflammation (drug therapy)
  • NF-E2-Related Factor 2 (metabolism)
  • Oxidative Stress (drug effects)
  • PC12 Cells
  • Protective Agents (pharmacology)
  • Rats

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