bims-noxint Biomed News
on NADPH oxidases in tumorigenesis
Issue of 2020‒03‒22
four papers selected by
Laia Caja Puigsubira
Uppsala University

  1. Pain. 2020 Apr;161(4): 758-772
    Xu J, Wei X, Gao F, Zhong X, Guo R, Ji Y, Zhou X, Chen J, Yao P, Liu X, Wei X.
      High-frequency stimulation (HFS) of the sciatic nerve has been reported to produce long-term potentiation (LTP) and long-lasting pain hypersensitivity in rats. However, the central underlying mechanism remains unclear. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) belongs to a group of electron-transporting transmembrane enzymes that produce reactive oxygen species (ROS). Here, we found that NOX2 was upregulated in the lumbar spinal dorsal horn after HFS of the left sciatic nerve, which induced bilateral pain and spinal LTP in both male and female rats. Blocking NOX2 with blocking peptide or shRNA prevented the development of bilateral mechanical allodynia, the induction of spinal LTP, and the phosphorylation of N-methyl-d-aspartate (NMDA) receptor 2B (GluN2B) and nuclear factor kappa-B (NF-κB) p65 after HFS. Moreover, NOX2 shRNA reduced the frequency and amplitude of both spontaneous excitatory postsynaptic currents and miniature excitatory postsynaptic currents in laminar II neurons. Furthermore, 8-hydroxyguanine (8-OHG), an oxidative stress marker, was increased in the spinal dorsal horn. Spinal application of ROS scavenger, Phenyl-N-tert-butylnitrone (PBN), depressed the already established spinal LTP. Spinal application of H2O2, one ROS, induced LTP and bilateral mechanical allodynia, increased the frequency and amplitude of spontaneous excitatory postsynaptic currents in laminar II neurons, and phosphorylated GluN2B and p65 in the dorsal horn. This study provided electrophysiological and behavioral evidence that NOX2-derived ROS in the spinal cord contributed to persistent mirror-image pain by enhancing the synaptic transmission, which was mediated by increasing presynaptic glutamate release and activation of NMDA receptor and NF-κB in the spinal dorsal horn.
  2. BMC Pediatr. 2020 Mar 18. 20(1): 127
    Loffredo L, Spalice A, Salvatori F, De Castro G, Guido CA, Zicari AM, Ciacci P, Battaglia S, Brindisi G, Ettorre E, Nocella C, Salvatori G, Duse M, Violi F, Carnevale R.
      BACKGROUND: Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) identifies patients with acute onset of obsessive-compulsive and tic disorders. The objective of this study was to evaluate serum NOX2 levels, as well as 8-iso-prostaglandin F2α (8-iso-PGF2α) and lipopolysaccharide (LPS) of PANDAS patients.METHODS: In this study we wanted to compare serum levels of soluble NOX2-dp (sNOX-2-dp), iso-PGF2α and LPS in 60 consecutive subjects, including 30 children affected by PANDAS and 30 controls (CT) matched for age and gender. Serum zonulin was used as intestinal permeability assay.
    RESULTS: Compared with CT, PANDAS children had increased serum levels of sNOX-2-dp, 8-iso-PGF2α and LPS. Bivariate analysis showed that serum sNOX2-dp was significantly correlated with LPS (Rs = 0.359; p = 0.005), zonulin (Rs = 0.444; p < 0.001) and 8-iso-PGF2α (Rs = 0.704; p < 0.001). Serum LPS significantly correlated with zonulin (Rs = 0.610; p < 0.001), and 8-iso-PGF2α (Rs = 0.591; p = 0.001). Finally, a multiple linear regression analysis showed that serum 8-iso-PGF2α and zonulin were the only independent variables associated with sNOX2-dp (R2 = 68%).
    CONCLUSION: This study shows that children affected by PANDAS have high circulating levels of sNOX2-dp, isoprostanes and of LPS that could be involved in the process of neuroinflammation.
    Keywords:  LPS; NADPH oxidase; NOX2; Oxidative stress; PANDAS; PANS
  3. Asian J Neurosurg. 2020 Jan-Mar;15(1):15(1): 10-15
    Parastan RH, Christopher M, Torrys YS, Mahadewa TGB.
      Traumatic brain injury is caused by physical collision (primary injury). It changes the brain's biochemistry and disturbs the normal brain function such as memory loss and consciousness disturbance (secondary injury). The severity can be measured with the Glasgow Coma Scale. The secondary injury will cause oxidative stress that leads to the nervous cells death, so treatment is needed before it gets worse. Primary injury results in excess of reactive oxidative stress (ROS) which is known from NADPH oxidase 2 (Nox2). Excessive ROS is deadly to the nerve cells. Excessive ROS will activate nuclear factor erythroid 2-like 2 (Nrf2). Nrf2 will bind to antioxidant response elements, to protect multi organs against ROS, including this brain injury. However, this does not last long, so it requires handling excess ROS. Apocynin can inhibit the activation of Nox2, and reduce the neuron injuries in the hippocampus. It also protects the tissues from oxidative stress. While Nrf2 can be activated by tert-butylhydroquinone, to protect cells. The combination may reduce the secondary brain injury, improve the neurologic recovery, cognitive function, and reduce the secondary cortical lesion.
    Keywords:  Apocynin; NADPH oxidase 2; nuclear factor erythroid 2-like 2; tert-butylhydroquinone; traumatic brain injury
  4. Biomolecules. 2020 Mar 09. pii: E422. [Epub ahead of print]10(3):
    Dec K, Łukomska A, Skonieczna-Żydecka K, Jakubczyk K, Tarnowski M, Lubkowska A, Baranowska-Bosiacka I, Styburski D, Skórka-Majewicz M, Maciejewska D, Gutowska I.
      Exposure of neural cells to harmful and toxic factors promotes oxidative stress, resulting in disorders of metabolism, cell differentiation, and maturation. The study examined the brains of rats pre- and postnatally exposed to sodium fluoride (NaF 50 mg/L) and activity of NADPH oxidase 4 (NOX4), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), concentration of glutathione (GSH), and total antioxidant capacity (TAC) in the cerebellum, prefrontal cortex, hippocampus, and striatum were measured. Additionally, NOX4 expression was determined by qRT-PCR. Rats exposed to fluorides (F-) showed an increase in NOX4 activity in the cerebellum and hippocampus, a decrease in its activity in the prefrontal cortex and hippocampus, and upregulation of NOX4 expression in hippocampus and its downregulation in other brain structures. Analysis also showed significant changes in the activity of all antioxidant enzymes and a decrease in TAC in brain structures. NOX4 induction and decreased antioxidant activity in central nervous system (CNS) cells may be central mechanisms of fluoride neurotoxicity. NOX4 contributes to blood-brain barrier damage, microglial activation, and neuronal loss, leading to impairment of brain function. Fluoride-induced oxidative stress involves increased reactive oxygen speciaes (ROS) production, which in turn increases the expression of genes encoding pro-inflammatory cytokines.
    Keywords:  GSH; NOX4; brain; fluoride; neurotoxicity; oxidative stress