Carnosine prevents necrotic and apoptotic death of rat thymocytes via ouabain‐sensitive Na/K‐ATPase

Abstract

It is known that ouabain, a selective inhibitor of Na/K-ATPase, can cause not only activation of signal cascades, which regulate the cell viability, but also can cause free radical accumulation, which can evoke the oxidative stress. We have shown that nanomolar concentrations of ouabain result in the temporary increase in the level of intracellular free radicals but the millimolar concentration of ouabain induces a stable intracellular accumulation of free radicals in rat thymocytes. The increasing level of free radicals resulting from both low and high concentrations of ouabain can be attenuated by the antioxidant, carnosine. Moreover the long-term incubation with ouabain leads to the cell death by necrosis and apoptosis. Ouabain-mediated apoptosis and necrosis were also abolished by carnosine.

Much More than a Cardiotonic Steroid: Modulation of Inflammation by Ouabain

“…It was also observed that this effect is related to CD69 increased expression, a molecule associated with cell activation, induced by ouabain (Rodrigues-Mascarenhas et al, 2003 ). Additionally, ouabain induces in vitro intracellular free radicals accumulation and thymocytes death (Smolyaninova et al, 2013 ). In vivo , ouabain synergizes with hydrocortisone increasing T lymphocyte precursors death by apoptosis (Rodrigues-Mascarenhas et al, 2006 ), which reinforces its role as a stress-related hormone.…”