Redox regulation of cell survival by the thioredoxin superfamily: an implication of redox gene therapy in the heart.
Reactive oxygen species (ROS) are the key mediators of pathogenesis in cardiovascular diseases. Members of the thioredoxin superfamily take an active part in scavenging reactive oxygen species, thus playing an essential role in maintaining the intracellular redox status. The alteration in the expression levels of thioredoxin family members and related molecules constitute effective biomarkers in various diseases, including cardiovascular complications that involve oxidative stress. Thioredoxin, glutaredoxin, peroxiredoxin, and glutathione peroxidase, along with their isoforms, are involved in interaction with the members of metabolic and signaling pathways, thus making them attractive targets for clinical intervention. Studies with cells and transgenic animals have supported this notion and raised the hope for possible gene therapy as modern genetic medicine. Of all the molecules, thioredoxins, glutaredoxins, and peroxiredoxins are emphasized, because a growing body of evidence reveals their essential and regulatory role in several steps of redox regulation. In this review, we discuss some pertinent observations regarding their distribution, structure, functions, and interactions with the several survival- and death-signaling pathways, especially in the myocardium.
Ahsan
Md Kaimul
MK
Cardiovascular Research Center, Department of Surgery, School of Medicine, University of Connecticut Health Center , Farmington, CT 06030-1110, USA. ddas@neuron.uchc.edu
Lekli
Istvan
I
Ray
Diptarka
D
Yodoi
Junji
J
Das
Dipak K
DK
D000818:Animals; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D015316:Genetic Therapy; D054477:Glutaredoxins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013879:Thioredoxins / Q000378:metabolism / Q000502:physiology*
D054477:Glutaredoxins; D013879:Thioredoxins; D054464:Peroxiredoxins