Protection Against Reperfusion-Induced Arrhythmias by Human Thioredoxin

Abstract

Adult T-cell leukemia-derived factor (ADF), identified in the supernatant of adult T-cell leukemia (ATL) cell culture, is a human homologue of thioredoxin and consists of 104 amino acids; it has two redox-active half-cysteine residues in an exposed active center. Human thioredoxin has many biological activities, including growth promotion, cell activation, and a catalase-like radical scavenging activity. We examined the protective effect of human thioredoxin (h-thioredoxin) against reperfusion-induced arrhythmias in an isolated rat heart model with 10-min regional ischemia followed by 30-min reperfusion. Male Wistar rats were assigned to six groups: a control, a superoxide dismutase (SOD 8 x 10(4) IU/L), and a catalase group (1 x 10(6) IU/L), and three groups treated with h-thioredoxin [approximately .01 microM (TRX-I group), approximately 0.1 microM (TRX-II group), and approximately 1 microM (TRX-III group)]. In the early reperfusion period, h-thioredoxin reduced the incidence of ventricular fibrillation (VF) to 8% in the TRX-II group (p < 0.01) from the control value of 75%. SOD and catalase reduced the incidence of VF to 43 and 33%, respectively (NS). During the entire reperfusion period, the incidence of VF in the SOD group was 79%, as compared to 83% in the control group. In the catalase and TRX-II groups, the incidence of VF was significantly reduced to 42 and 25%, respectively. These findings indicate that SOD failed to protect against the reperfusion-induced arrhythmias. h-Thioredoxin exerted a protective effect against these arrhythmias; a concentration of approximately 0.1 micro was the most effective.

Chronic elevation of plasma thioredoxin: Inhibition of chemotaxis and curtailment of life expectancy in AIDS

“…Several studies, for example, have already reported that injection of a bolus of Trx substantially prevents ischemic reperfusion injury (15)(16)(17)(18). These findings were previously ascribed to the reducing power of Trx and its ability to remove locally generated reactive oxygen intermediates.…”

“…It is induced by oxidative stress (8,11), is translocated into the nucleus in stressed cells (8,11), is chemotactic in vitro for eosinophils (7), and effectively blocks ischemic injury (15)(16)(17)(18). In addition, our recent studies show that Trx has potent in vitro and in vivo chemoattractant activity for murine neutrophils, monocytes, and lymphocytes (9).…”

Selective activation of oxidized PTP1B by the thioredoxin system modulates PDGF-β receptor tyrosine kinase signaling

“…On the basis of the identification of TrxR1-mediated control of growth factor signaling, it will be highly interesting to investigate whether alterations in TrxR1 levels or activity, as observed for example in an animal model of liver cancer (54) and arrhythmia (63), are associated with etiologically relevant alterations in growth factor and receptor tyrosine kinase signaling.…”

Serum Thioredoxin (TRX) Levels in Patients With Heart Failure

“…27 TRX expression is upregulated during the acute stage in rats with giant cell myocarditis, and the development of acute immune-mediated myocarditis may be regulated by the cellular redox state via TRX. 28 Recombinant TRX protected against reperfusion injury in an ischemic lung model 29 and against reperfusion-induced arrhythmias in an isolated rat heart model, 4 and overexpression of TRX in transgenic mice attenuated focal ischemic brain damage. 15 Taken together, these data indicate that TRX protects organs from the cytotoxicity caused by ROS.…”

“…14,15 Moreover, TRX eliminates hydrogen peroxide and acts as a radical scavenger, and recombinant TRX has a protective activity against hydrogen peroxide cytotoxicity, in which the generation of ROS seems to be involved. 14,16 TRX suppressed reperfusion-induced arrhythmias in an isolated rat heart model, 4 and overexpression of TRX in transgenic mice was protective for postischemic reperfusion injury in the brain in vivo. 17 However, the levels of TRX that regulate the cellular redox state have not been investigated in human patients with heart diseases.…”