Traumatic brain injury and NADPH oxidase: A deep relationship

Traumatic brain injury (TBI) represents one of the major causes of mortality and disability in the world. TBI is characterized by primary damage resulting from the mechanical forces applied to the head as a direct result of the trauma and by the subsequent secondary injury due to a complex cascade of biochemical events that eventually lead to neuronal cell death. Oxidative stress plays a pivotal role in the genesis of the delayed harmful effects contributing to permanent damage. NADPH oxidases (Nox), ubiquitary membrane multisubunit enzymes whose unique function is the production of reactive oxygen species (ROS), have been shown to be a major source of ROS in the brain and to be involved in several neurological diseases. Emerging evidence demonstrates that Nox is upregulated after TBI, suggesting Nox critical role in the onset and development of this pathology. In this review, we summarize the current evidence about the role of Nox enzymes in the pathophysiology of TBI

Traumatic brain injury and NADPH oxidase: A deep relationship

Traumatic brain injury (TBI) represents one of the major causes of mortality and disability in the world. TBI is characterized by primary damage resulting from the mechanical forces applied to the head as a direct result of the trauma and by the subsequent secondary injury due to a complex cascade of biochemical events that eventually lead to neuronal cell death. Oxidative stress plays a pivotal role in the genesis of the delayed harmful effects contributing to permanent damage. NADPH oxidases (Nox), ubiquitary membrane multisubunit enzymes whose unique function is the production of reactive oxygen species (ROS), have been shown to be a major source of ROS in the brain and to be involved in several neurological diseases. Emerging evidence demonstrates that Nox is upregulated after TBI, suggesting Nox critical role in the onset and development of this pathology. In this review, we summarize the current evidence about the role of Nox enzymes in the pathophysiology of TBI

Aquaporins can facilitate Nox-produced hydrogen peroxide transport through plasma membrane in leukaemia cell lines

Reactive oxygen species (ROS) can act as messengers in cellular signalling transduction pathways and it is now firmly established that an increase of ROS (particularly hydrogen peroxide) supports cellular growth and proliferation contributing to cancer development. Hydrogen peroxide has been long thought to be freely diffusible but recent evidence demonstrated that transport of H2O2 across membranes is tightly regulated [1]. Furthermore, it has been recently reported that a specific mammalian aquaporin homologue (AQP8) possess the capacity to channel H2O2 across membranes [2] and that AQP3 expression modulate the intracellular level of H2O2 in human cells and is necessary for Nox-derived H2O2 signalling [3]. The aim of this study was to assess whether specific aquaporin isoforms can channel Nox-produced H2O2 across the plasma membrane affecting downstream pathways linked to cell proliferation in leukaemia cells. The expression of AQP8 was assessed and verified by Western Blot and PCR in HL60 and B1647 cell lines. We showed that aquaporin inhibition caused a decrease in intracellular ROS accumulation both when H2O2 was produced by Nox enzymes and when it was added exogenously to the medium. In addition, intracellular hydrogen peroxide transport was evaluated by using a boronate-based fluorescent probe selective for H2O2 (PF1) and the data obtained confirmed that aquaporin inhibition decreased the intracellular level of H2O2. As we previously demonstrated that Nox-generated ROS sustain glucose uptake and cellular proliferation in leukemic cell lines [4, 5], in this study we report that treatment with aquaporin inhibitor caused a significant decrease in glucose transport in HL60 and B1647 cells. These results suggest that aquaporins are able to transport Nox-generated H2O2 across the plasma membrane and to affect downstream pathways in leukaemia cells