Peroxide detoxification by brain cells

Abstract

Peroxides are generated continuously in cells that consume oxygen. Among the different peroxides, hydrogen peroxide is the molecule that is formed in highest quantities. In addition, organic hydroperoxides are synthesized as products of cellular metabolism. Generation and disposal of peroxides is a very important process in the human brain, because cells of this organ consume 20% of the oxygen used by the body. To prevent cellular accumulation of peroxides and damage generated by peroxide-derived radicals, brain cells contain efficient antioxidative defense mechanisms that dispose of peroxides and protect against oxidative damage. Cultured brain cells have been used frequently to investigate peroxide metabolism of neural cells. Efficient disposal of exogenous hydrogen peroxide was found for cultured astrocytes, oligodendrocytes, microglial cells, and neurons. Comparison of specific peroxide clearance rates revealed that cultured oligodendrocytes dispose of the peroxide quicker than the other neural cell cultures. Both catalase and the glutathione system contribute to the clearance of hydrogen peroxide by brain cells. For efficient glutathione-dependent reduction of peroxides, neural cells contain glutathione in high concentration and have substantial activity of glutathione peroxidase, glutathione reductase, and enzymes that supply the NADPH required for the glutathione reductase reaction. This article gives an overview on the mechanisms involved in peroxide detoxification in brain cells and on the capacity of the different types of neural cells to dispose of peroxides.

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

“…37 These results suggest that rotenone exposure enhanced the levels of pro-oxidative and antioxidative enzymes in glial cells. In addition, 24 hours after exposure to rotenone, the levels of glutathione (ie, GSH), a prominent antioxidant, were higher in rotenone-treated microglia than in mocktreated cells ( Figure 5C).…”

“…Unlike neurons, exposure to rotenone was not toxic to microglia, in either the presence or the absence of neurons; however, rotenone-treated microglia adopted a distinct activated form, indicating that microglia could actively respond to rotenone exposure. Studies 37,47 have shown that activated microglia release numerous inflammatory mediators, such as NO and superoxide, and produce antioxidants to successfully defend the CNS against threats to the brain. Microglia are equipped with efficient antioxidative defense mechanisms to prevent oxidative damage that would compromise their function.…”

Oxidative stress and modification of synaptic proteins in hippocampus after traumatic brain injury

“…Moreover, GPx and CAT participate in the elimination of H 2 O 2 , which is one of the most toxic molecules in the brain. Because GPx and CAT both control H 2 O 2 , they represent the major defense against ROS [14]. Decreased activity of Mn-SOD is a likely consequence of peroxynitrite after TBI, and could lead to further oxidative stress and progressively enhance peroxynitrite production as part of the secondary damage cascade [10].…”

“…and H 2 O 2 crosses the normal threshold, the system becomes compromised. Catalase and glutathione peroxidase (GPx), acting in concert with superoxide dismutase (SOD), constitute the major defense enzymes against superoxide radicals [13,14]. Analysis of these antioxidants, products of LPO and protein damage, may a yield snapshot of oxidative stress.…”

Supportive or detrimental roles of P2Y receptors in brain pathology?—The two faces of P2Y receptors in stroke and neurodegeneration detected in neural cell and in animal model studies

“…Oxidative stress is regarded as a factor contributing to inducement of the PTP and apoptosis [35,37,38]. Cells have antioxidant tools to degrade ROS, including SOD, catalase, glutathione peroxidase, and thioredoxins [39][40][41][42]. In many cases, it is still under debate whether ROS are the cause or consequence of neurodegenerative diseases.…”