Role of sulforaphane in endoplasmic reticulum homeostasis through regulation of the antioxidant response

Life Sci. 2022 Jun 15:299:120554. doi: 10.1016/j.lfs.2022.120554. Epub 2022 Apr 19.

Abstract

Nowadays, the nutraceutical agent sulforaphane (SFN) shows great versatility in turning on different cellular responses. Mainly, this isothiocyanate acts as a master regulator of cellular homeostasis due to its antioxidant response and cytoplasmic, mitochondrial, and endoplasmic reticulum (ER) protein modulation. Even more, SFN acts as an effective strategy to counteract oxidative stress, apoptosis, and ER stress, among others as seen in different injury models. Particularly, ER stress is buffered by the unfolded protein response (UPR) activation, which is the first instance in orchestrating the recovery of ER function. Interestingly, different studies highlight a close interrelationship between ER stress and oxidative stress, two events driven by the accumulation of reactive oxygen species (ROS). This response inevitably perpetuates itself and acts as a vicious cycle that triggers the development of different pathologies, such as cardiovascular diseases, neurodegenerative diseases, and others. Accordingly, it is vital to target ER stress and oxidative stress to increase the effectiveness of clinical therapies used to treat these diseases. Therefore, our study is focused on the role of SFN in preserving cellular homeostasis balance by regulating the ER stress response through the Nrf2-modulated antioxidant pathway.

Keywords: 1,2-dithio-3-thione; 6-hydroxydopamine; Dithiothreitol; Endoplasmic reticulum stress; Hydrogen peroxide; Nrf2; Oxidative stress; Reactive oxygen species; Sulforaphane; Thapsigargin; Tunycamicin.

Publication types

  • Review

MeSH terms

  • Antioxidants* / metabolism
  • Antioxidants* / pharmacology
  • Apoptosis
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum Stress / physiology
  • Homeostasis
  • Isothiocyanates* / metabolism
  • Isothiocyanates* / pharmacology
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism
  • Sulfoxides
  • Unfolded Protein Response

Substances

  • Antioxidants
  • Isothiocyanates
  • Reactive Oxygen Species
  • Sulfoxides
  • sulforaphane