Reactive oxygen species are key mediators of the nitric oxide

LI MACHIAVELLI; AH B POLIANDRI; AF QUINTEROS; JP CABILLA; BH DUVILANSKI

NITRIC OXIDE-BIOLOGY AND CHEMISTRY

Elsevier

Año: 2007 vol. 16 p. 237 - 246

1089-8603

We previously showed that long-term exposure of anterior pituitary cells to nitric oxide (NO) induces apoptosis. The intracellular signalsunderlying this eVect remained unclear. In this study, we searched for possible mechanisms involved in the early stages of the NOapoptotic cascade. Caspase 3 was activated by NO with no apparent disruption of mitochondrial membrane potential. NO caused a rapidincrease of reactive oxygen species (ROS), and this increase seems to be dependent of mitochondrial electron transport chain. The antioxidantN-acetyl-cysteine avoided ROS increase, prevented the NO-induced caspase 3 activation, and reduced the NO apoptotic eVect. Catalasewas inactivated by NO, while glutathione peroxidase (GPx) activity and reduced glutathione (GSH) were not modiWed at Wrst, butincreased at later times of NO exposure. The increase of GSH level is important for the scavenging of the NO-induced ROS overproduction.Our results indicate that ROS have an essential role as a trigger of the NO apoptotic cascade in anterior pituitary cells. The permanentinhibition of catalase may strengthen the oxidative damage induced by NO. GPx activity and GSH level augment in response to theoxidative damage, though this increase seems not to be enough to rescue the cells from the NO effect.