Protection against HEMA-Induced Mitochondrial Injury In Vitro by Nrf2 Activation

Oxid Med Cell Longev. 2019 Apr 7:2019:3501059. doi: 10.1155/2019/3501059. eCollection 2019.

Abstract

Dental resin monomers such as 2-hydroxyethyl methacrylate (HEMA) disturb vital cell functions and induce mitochondrial intrinsic apoptosis via generation of oxidative stress. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the gene expression of antioxidative enzymes and plays a crucial role in the maintenance of cellular redox equilibrium and mitochondrial homeostasis. The present study investigated the functional significance of Nrf2 in cellular response toward HEMA. It was found that HEMA stimulation promoted nuclear translocation of Nrf2 and increased Nrf2 and heme oxygenase-1 (HO-1) expression, which was further enhanced by Nrf2 activator tert-butylhydroquinone (tBHQ), but suppressed by Nrf2 inhibitor ML385. Pretreatment of primary human dental pulp cells (hDPCs) with tBHQ protected the cells from HEMA-induced oxidative injury (increased reactive oxygen species production and apoptosis) and mitochondrial impairment (morphological alterations, decreased ATP production, suppressed oxidative phosphorylation activity, depolarization of mitochondrial membrane potential, and disrupted electron transport chain). In contrast, pretreatment with ML385 increased cell sensitivity to these injurious processes. This protective effect on mitochondria could be related to peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α)/nuclear respiratory factor 1 (NRF1) pathway. These results contribute to the understanding of the function of Nrf2 and the development of novel therapies to counteract the adverse effects of dental resin monomers.

MeSH terms

  • Adolescent
  • Adult
  • Apoptosis / drug effects
  • Dental Pulp / pathology
  • Dental Pulp / ultrastructure
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Hydroquinones / pharmacology
  • Methacrylates / toxicity*
  • Mitochondria / drug effects
  • Mitochondria / pathology*
  • Mitochondria / ultrastructure
  • Models, Biological
  • NF-E2-Related Factor 2 / metabolism*
  • Nuclear Respiratory Factor 1 / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Protective Agents / metabolism*
  • Reactive Oxygen Species / metabolism
  • Young Adult

Substances

  • Hydroquinones
  • Methacrylates
  • NF-E2-Related Factor 2
  • NRF1 protein, human
  • Nuclear Respiratory Factor 1
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Protective Agents
  • Reactive Oxygen Species
  • hydroxyethyl methacrylate
  • 2-tert-butylhydroquinone
  • Heme Oxygenase-1