Selenoprotein T as a new positive inotrope in the goldfish Carassius auratus

Abstract

Selenoprotein T (SELENOT) is a thioredoxin-like protein, which mediates oxidoreductase functions via its redox active motif Cys-X-X-Sec. In mammals, SELENOT is expressed during ontogenesis and progressively decreases in adult tissues. In the heart, it is re-expressed after ischemia and induces cardioprotection against ischemia/reperfusion (I/R) injury. SELENOT is present in teleost fish, including the goldfish Carassius auratus. This study aimed to evaluate the cardiac expression of SELENOT, and the effects of exogenous PSELT (a 43-52 SELENOT derived-peptide) on the heart function of C. auratus, a hypoxia tolerance fish model. We found that SELENOT was expressed in cardiac extracts of juvenile and adult fish, located in the sarcoplasmic reticulum (SR) together with calsequestrin-2. Expression increased under acute hypoxia. On ex vivo isolated and perfused goldfish heart preparations, under normoxia, PSELT dose-dependently increased Stroke Volume (SV), Cardiac Output (Q̇), and Stroke Work (SW), by involving cAMP, PKA, L-type calcium channels, SERCA2a pumps, and pAkt. Under hypoxia, PSELT did not affect myocardial contractility. Only at higher concentrations (10−8 -10−7 M) an increase of SV and Q̇ was observed. It also reduced the cardiac expression of 3-NT, a tissue marker of nitrosative stress which increases under low oxygen availability. These data are the first to propose SELENOT 43-52, PSELT, as a cardiac modulator in fish, with a potential protective role under hypoxia.