INTRODUCCIÓN: REVISIÓN CRITICA DEL PROBLEMA

CAPÍTULO IX
Without discard other possible mechanisms, the incremented ROS production with
HSA+SP600125 and the decreased ROS production with gHSA+SP600125 can
be explained by the uncoupling of eNOS by gHSA. That is, AP-1 inhibition with
SP600125 induced down-regulation of eNOS and up-regulation of NADPH
oxidase expression leading to an enhanced ROS production. This is the normal
situation in the presence of HSA. However, AP-1 inhibition in the presence of
gHSA resulted in a partial reduction of the gHSA-enhanced ROS production. This
happens because, as we have shown, gHSA uncoupled eNOS, which in this
situation produces superoxide anion instead of NO. So, part of the gHSA-induced
ROS production came from the uncoupled eNOS (Figure 6). Therefore, down-
regulation of eNOS by SP600125 in these conditions will partially reduce ROS
production whereas the up-regulating effect of SP600125 on NADPH oxidase
expression overlaps the gHSA activation of the same genes resulting in a null
increase of the net ROS production.
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