Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Reductive stress linked to small HSPs, G6PD, and Nrf2 pathways in heart disease. Antioxid Redox Signal 2013 Mar 20;18(9):1114-27

Date

09/04/2012

Pubmed ID

22938199

Pubmed Central ID

PMC3567781

DOI

10.1089/ars.2012.4914

Scopus ID

2-s2.0-84874052914   67 Citations

Abstract

SIGNIFICANCE: Aerobic organisms must exist between the dueling biological metabolic processes for energy and respiration and the obligatory generation of reactive oxygen species (ROS) whose deleterious consequences can reduce survival. Wide fluctuations in harmful ROS generation are circumvented by endogenous countermeasures (i.e., enzymatic and nonenzymatic antioxidants systems) whose capacity decline with aging and are enhanced by disease states.

RECENT ADVANCES: Substantial efforts on the cellular and molecular underpinnings of oxidative stress has been complemented recently by the discovery that reductive stress similarly predisposes to inheritable cardiomyopathy, firmly establishing that the biological extremes of the redox spectrum play essential roles in disease pathogenesis.

CRITICAL ISSUES: Because antioxidants by nutritional or pharmacological supplement to prevent or mitigate disease states have been largely disappointing, we hypothesize that lack of efficacy of antioxidants might be related to adverse outcomes in responders at the reductive end of the redox spectrum. As emerging concepts, such as reductive, as opposed, oxidative stress are further explored, there is an urgent and critical gap for biochemical phenotyping to guide the targeted clinical applications of therapeutic interventions.

FUTURE DIRECTIONS: New approaches are vitally needed for characterizing redox states with the long-term goal to noninvasively assess distinct clinical states (e.g., presymptomatic, end-stage) with the diagnostic accuracy to guide personalized medicine.

Author List

Brewer AC, Mustafi SB, Murray TV, Rajasekaran NS, Benjamin IJ

Author

Ivor J. Benjamin MD Center Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acetylcysteine
Animals
Antioxidants
Catalase
Disease Models, Animal
Early Diagnosis
Glucosephosphate Dehydrogenase
Glutathione
Heart Diseases
Heat-Shock Proteins
Humans
Mice
Models, Cardiovascular
NF-E2-Related Factor 2
Neoplasm Proteins
Peroxidases
Precision Medicine
Reactive Nitrogen Species
Reactive Oxygen Species
Recombinant Fusion Proteins
Superoxide Dismutase
Thioredoxins
alpha-Crystallin B Chain
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a