Reactive oxygen species overproduction

The above data suggest an important role of reactive oxygen species in the development of heart diseases. This suggestion has been supported by many studies, which also demonstrated a potential efficacy of antioxidants, free scavengers, and chelators in the treatment of these diseases. Mitochondrial oxygen radical overproduction can probably be one of the critical causes. 

In general, oxidative and nitrosative stress result from an imbalance between an overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) on one side and a deficiency of enzymatic and... 

Mitochondrial oxidative stress and mitochondrial GSH defense affects transcription factor activation. Oxidant stress in mitochondria not only can promote the loss of mitochondrial GSH and mitochondrial functions, but also can promote extramito-chondrial activation of NF-kB and therefore may affect nuclear gene expression. Mitochondria are targets of cytokines leading to the overproduction of reactive oxygen species induced by ceramide, a lipid intermediate of cytokine action and closely associated with apoptosis. Chronic ethanol intake depletes liver mitochondrial glutathione due to an ethanol-induced defect in the transport of GSH from cytosol into the mitochondrial matirix. This sensitizes liver cells to the prooxidant effects of cytokines and prooxidants generated by the oxidative metabolism of ethanol. 

Although the mechanisms of necrotic cell death downstream of RIPl are mostly unclear, inhibition of certain cell-signaling pathways has been found to attenuate necroptotic cell death. Overproduction of reactive oxygen species (ROS) is a hallmark of necrotic cell death and is a prominent part of necroptosis in some systems (161). ROS production in conditions of... 

Under these conditions apoptosis was not affected by either reactive oxygen species scavengers or inhibitors of reactive oxygen species scavengers. Furthermore, studies of apoptosis in a fibroblast cell line lacking intact mitochondia suggest that neither mitochondrial respiration nor oxidative phosphorylation are required for the induction of apoptosis or for Bcl-2-mediated protection (Jacobson et al., 1993). In this context, Bcl-2 overproduction does not affect intracellular ATP levels or O2 consumption in PC 12 cells (Mah et al.,... 

Heat stress is an environmental factor responsible for oxidative stress. We reported that reactive oxygen species (ROS) production by mitochondria was significantly increased in skeletal muscle of birds after exposure to heat stress (Mujahid et al., 2007), and that muscle mitochondria from heat-stressed birds also had the higher mitochondrial membrane potential (AT) (M. Kikusato, unpublished data). These results implied that the overproduction of ROS may depend on AT. We also found that heat stress significantly decreased avian uncoupling protein (avUCP) in muscle mitochondria (Mujahid et al., 2009). Therefore, this decrease may contribute to excess ROS production, possibly via a depression of inducible proton leak. To elucidate more precisely the mechanism involved in the overproduction of mitochondrial ROS under heat stress conditions, we have attempted to clarify how heat stress-induced ROS production depends on AT, and to evaluate the effect of avUCP downregulation on the inducible proton leak. 

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