Thioredoxin 1 (TRX1) overexpression cancels the slow force response (SFR) development

ZAVALA MR; GELPI RJ; DÍAZ RG; VILLA-ABRILLE MC; DONATO M; PÉREZ NG

Ciudad Autónoma de Buenos Aires

Congreso; XXII International Society for Heart Research (ISHR) World Congress; 2016

International Society for Heart Research (ISHR)

(In Press at May 2016)The stretch of cardiac muscle increases developed force in two phases. The first phase occurs immediately after stretch and is the expression of the Frank-Starling mechanism, while the second one or slow force response (SFR) occurs gradually and is due to an increase in the calcium transient amplitude. An important step in the chain of events leading to the SFR generation is the increased production of reactive oxygen species (ROS) leading to redox sensitive ERK1/2, p90RSK and NHE1 phosphorylation/activation. Conversely, suppression of ROS production blunts the SFR. The purpose of this study was to verify whether overexpression of the ubiquitously expressed antioxidant molecule TRX1 affects the SFR development and NHE1 phosphorylation. We did not detect any change in basal phopho-ERK1/2, phopho-p90RSK and NHE1 expression in mice with TRX1 overexpression compared to wild-type (pERK1/2:105.4±9.9%, n=4; p-p90RSK: 111±15%, n=3; NHE1:100±13%, n=4, ns) Isolated mouse papillary muscles (wild-type, WT, or with TRX1 overexpression) were stretched from 92 to 98 % of Lmax. The SFR was 137±1% of the initial rapid phase in wild-type mice (n=8, P