Antioxidants & redox signaling
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Antioxid. Redox Signal. · Feb 2009
ReviewModulation of brain hemichannels and gap junction channels by pro-inflammatory agents and their possible role in neurodegeneration.
In normal brain, neurons, astrocytes, and oligodendrocytes, the most abundant and active cells express pannexins and connexins, protein subunits of two families forming membrane channels. Most available evidence indicates that in mammals endogenously expressed pannexins form only hemichannels and connexins form both gap junction channels and hemichannels. Whereas gap junction channels connect the cytoplasm of contacting cells and coordinate electric and metabolic activity, hemichannels communicate the intra- and extracellular compartments and serve as a diffusional pathway for ions and small molecules. ⋯ If the stimulus is sufficiently deleterious, microglia become overactivated and release bioactive molecules that increase the activity of hemichannels and reduce gap junctional communication in astroglial networks, depriving neurons of astrocytic protective functions, and further reducing neuronal viability. Continuous glial activation triggered by low levels of anomalous proteins expressed in several neurodegenerative diseases induce glial hemichannel and gap junction channel disorders similar to those of acute inflammatory responses triggered by ischemia or infectious diseases. These changes are likely to occur in diverse cell types of the CNS and contribute to neurodegeneration during inflammatory process.
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Antioxid. Redox Signal. · Jan 2009
Curcumin attenuates vascular inflammation and cerebral vasospasm after subarachnoid hemorrhage in mice.
Cerebral vasospasm is a major cause of death and disability after subarachnoid hemorrhage (SAH); however, clinical therapies to limit the development of cerebral vasospasm are lacking. Although the causative factors underlying the development of cerebral vasospasm are poorly understood, oxidative stress contributes to disease progression. ⋯ Despite the ability of curcumin to limit the development of cerebral vasospasm and secondary infarction, behavioral outcome was not improved, indicating a dissociation between cerebral vasospasm and neurologic outcome. Together, these data indicate a novel role for curcumin as a possible adjunct therapy after SAH, both to prevent the development of cerebral vasospasm and to reduce oxidative brain injury after secondary infarction.
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Antioxid. Redox Signal. · Nov 2008
ReviewOxidative stress in the regulation of normal and neoplastic hematopoiesis.
Recent evidence suggests that oxidative stress contributes significantly to the regulation of hematopoietic cell homeostasis. In particular, red blood cells and hematopoietic stem cells are highly sensitive to deregulated accumulation of reactive oxygen species (ROS). ⋯ Similarly, ROS buildup in hematopoietic stem cells compromises their function as a result of potential damage to their DNA leading to loss of quiescence and alterations of hematopoietic stem cell cycling. These abnormalities may lead to accelerated aging of hematopoietic stem cells or to hematopoietic malignancies.
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Mechanical ventilation (MV) is an indispensable therapy in the care of critically ill patients with acute lung injury and the acute respiratory distress syndrome; however, it is also known to further lung injury in certain conditions of mechanical stress, leading to ventilator-induced lung injury (VILI). The mechanisms by which conventional MV exacerbates lung injury and inflammation are of considerable clinical significance. ⋯ Here, we review the relevance of oxidative stress in VILI from human studies as well as cellular and mouse models of mechanical stress. Potential therapeutic avenues for the treatment of VILI with exogenous administration of antioxidants also are discussed.
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Antioxid. Redox Signal. · Oct 2007
ReviewOxygen, the lead actor in the pathophysiologic drama: enactment of the trinity of normoxia, hypoxia, and hyperoxia in disease and therapy.
Aerobic life has evolved a dependence on molecular oxygen for its mere survival. Mitochondrial oxidative phosphorylation absolutely requires oxygen to generate the currency of energy in aerobes. The physiologic homeostasis of these organisms is strictly maintained by optimal cellular and tissue-oxygenation status through complex oxygen-sensing mechanisms, signaling cascades, and transport processes. ⋯ Although the ROS are also required for many normal physiologic functions of the aerobes, overwhelming production of ROS coupled with their insufficient scavenging by endogenous antioxidants will lead to detrimental oxidative stress. Needless to say, molecular oxygen is at the center of oxygenation, oxidative phosphorylation, and oxidative stress. This review focuses on the biology and pathophysiology of oxygen, with an emphasis on transport, sensing, and activation of oxygen, oxidative phosphorylation, oxygenation, oxidative stress, and oxygen therapy.