The Type and Source of Reactive Oxygen Species Influences the Outcome of Oxidative Stress in Cultured Cells

Cells. 2021 Apr 30;10(5):1075. doi: 10.3390/cells10051075.

Abstract

Oxidative stress can be modeled using various different experimental approaches, such as exposing the cells or organisms to oxidative chemicals. However, the actual effects of these chemicals, outside of the immediate measured effect, have attracted relatively little attention. We show here that three commonly used oxidants, menadione, potassium bromate, and hydrogen peroxide, while known to function differently, also elicit different types of responses in HEK293T cells. Menadione and bromate exposure mainly trigger an integrated stress response, whereas hydrogen peroxide affects cellular processes more diversely. Interestingly, acute oxidative stress does not universally cause notable induction of DNA repair or antioxidant defense mechanisms. We also provide evidence that cells with previous experience of oxidative stress show adaptive changes in their responses when the stress is renewed. Our results urge caution when comparing studies where different sources of oxidative stress have been used or when generalizing the findings of these studies to other oxidant types or tissues.

Keywords: ATF4; DNA damage; RNA sequencing; bromate; hydrogen peroxide; integrated stress response; menadione; mitochondria; oxidative stress; unfolded protein response (UPR).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bromates / pharmacology
  • HEK293 Cells
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxidants / chemistry
  • Oxidants / pharmacology
  • Oxidants / standards*
  • Oxidative Stress*
  • Reactive Oxygen Species / metabolism*
  • Unfolded Protein Response
  • Vitamin K 3 / pharmacology

Substances

  • Bromates
  • Oxidants
  • Reactive Oxygen Species
  • potassium bromate
  • Vitamin K 3
  • Hydrogen Peroxide