Chemogenetic Approaches to Probe Redox Pathways: Implications for Cardiovascular Pharmacology and Toxicology

Annu Rev Pharmacol Toxicol. 2022 Jan 6:62:551-571. doi: 10.1146/annurev-pharmtox-012221-082339. Epub 2021 Sep 16.

Abstract

Chemogenetics refers to experimental systems that dynamically regulate the activity of a recombinant protein by providing or withholding the protein's specific biochemical stimulus. Chemogenetic tools permit precise dynamic control of specific signaling molecules to delineate the roles of those molecules in physiology and disease. Yeast d-amino acid oxidase (DAAO) enables chemogenetic manipulation of intracellular redox balance by generating hydrogen peroxide only in the presence of d-amino acids. Advances in biosensors have allowed the precise quantitation of these signaling molecules. The combination of chemogenetic approaches with biosensor methodologies has opened up new lines of investigation, allowing the analysis of intracellular redox pathways that modulate physiological and pathological cell responses. We anticipate that newly developed transgenic chemogenetic models will permit dynamic modulation of cellularredox balance in diverse cells and tissues and will facilitate the identification and validation of novel therapeutic targets involved in both physiological redox pathways and pathological oxidative stress.

Keywords: cardiac myocytes; endothelial cells; heart failure; hydrogen peroxide; oxidative stress; redox signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Hydrogen Peroxide* / metabolism
  • Hydrogen Peroxide* / pharmacology
  • Oxidation-Reduction
  • Oxidative Stress*
  • Signal Transduction

Substances

  • Hydrogen Peroxide