scholarly journals Melatonin Treatment Regulates SIRT3 Expression in Early Brain Injury (EBI) Due to Reactive Oxygen Species (ROS) in a Mouse Model of Subarachnoid Hemorrhage (SAH)

2018 ◽  
Vol 24 ◽  
pp. 3804-3814 ◽  
Author(s):  
Song Yang ◽  
Xiuping Chen ◽  
Shengli Li ◽  
Bin Sun ◽  
Chunhua Hang
Keyword(s):  
Reactive Oxygen Species ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Mouse Model ◽  
Reactive Oxygen ◽  
Early Brain Injury ◽  
Oxygen Species ◽  
Melatonin Treatment ◽  
Sirt3 Expression

scholarly journals SIRT3 Expression Decreases with Reactive Oxygen Species Generation in Rat Cortical Neurons during Early Brain Injury Induced by Experimental Subarachnoid Hemorrhage

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Wei Huang ◽  
Yong Huang ◽  
Ren-qiang Huang ◽  
Cheng-guang Huang ◽  
Wen-hao Wang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cerebral Cortex ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Cortical Neurons ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Early Brain Injury ◽  
Oxygen Species ◽  
Sirt3 Expression

Sirtuin3 (SIRT3) is an important protein deacetylase which predominantly presents in mitochondria and exhibits broad bioactivities including regulating energy metabolism and counteracting inflammatory effect. Since inflammatory cascade was proved to be critical for pathological damage following subarachnoid hemorrhage (SAH), we investigated the overall expression and cell-specific distribution of SIRT3 in the cerebral cortex of Sprague-Dawley rats with experimental SAH induced by internal carotid perforation. Results suggested that SIRT3 was expressed abundantly in neurons and endothelia but rarely in gliocytes in normal cerebral cortex. After experimental SAH, mRNA and protein expressions of SIRT3 decreased significantly as early as 8 hours and dropped to the minimum value at 24 h after SAH. By contrast, SOD2 expression increased slowly as early as 12 hours after experimental SAH, rose up sharply at the following 12 hours, and then was maintained at a higher level. In conclusion, attenuated SIRT3 expression in cortical neurons was associated closely with enhanced reactive oxygen species generation and cellular apoptosis, implying that SIRT3 might play an important neuroprotective role during early brain injury following SAH.

scholarly journals TAK1 mediates neuronal pyroptosis in early brain injury after subarachnoid hemorrhage

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Pengfei Xu ◽  
Chunrong Tao ◽  
Yuyou Zhu ◽  
Guoping Wang ◽  
Lingqi Kong ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Nlrp3 Inflammasome ◽  
Reactive Oxygen ◽  
Early Brain Injury ◽  
Potential Candidate ◽  
Oxygen Species

Abstract Background Innate immunity can facilitate early brain injury (EBI) following subarachnoid hemorrhage (SAH). Numerous studies suggest that pyroptosis could exacerbate extracellular immune responses by promoting secretion of inflammatory cytokines. Transforming growth factor-β-activated kinase 1 (TAK1) is a quintessential kinase that positively regulates inflammation through NF-κB and MAPK signaling cascades. However, the effects of TAK1 on neuroinflammation in EBI following SAH are largely unknown. Methods Two hundred and forty-six male C57BL/6J mice were subjected to the endovascular perforation model of SAH. A selective TAK1 inhibitor, 5Z-7-oxozeaenol (OZ) was administered by intracerebroventricular (i.c.v) injection at 30 min after SAH induction. To genetic knockdown of TAK1, small interfering RNA (siRNA) was i.c.v injected at 48 h before SAH induction. SAH grade, brain water content, BBB permeability, neurological score, western blot, real-time PCR, ELISA, transmission electron microscope, and immunofluorescence staining were performed. Long-term behavioral sequelae were evaluated by the rotarod and Morris water maze tests. Furthermore, OZ was added to the culture medium with oxyhemoglobin (OxyHb) to mimic SAH in vitro. The reactive oxygen species level was detected by DCFH-DA staining. Lysosomal integrity was assessed by Lyso-Tracker Red staining and Acridine Orange staining. Results The neuronal phosphorylated TAK1 expression was upregulated following SAH. Pharmacologic inhibition of TAK1 with OZ could alleviate neurological deficits, brain edema, and brain-blood barrier (BBB) disruption at 24 h after SAH. In addition, OZ administration restored long-term neurobehavioral function. Furthermore, blockade of TAK1 dampened neuronal pyroptosis by downregulating the N-terminal fragment of GSDMD (GSDMD-N) expression and IL-1β/IL-18 production. Mechanistically, both in vivo and in vitro, we demonstrated that TAK1 can induce neuronal pyroptosis through promoting nuclear translocation of NF-κB p65 and activating nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) inflammasome. TAK1 siRNA treatment mitigated SAH-induced neurobehavioral deficits and restrained phosphorylated NF-κB p65 expression and NLRP3 inflammasome activation. TAK1 blockade also ameliorated reactive oxygen species (ROS) production and prevented lysosomal cathepsin B releasing into the cytoplasm. Conclusions Our findings demonstrate that TAK1 modulates NLRP3-mediated neuronal pyroptosis in EBI following SAH. Inhibition of TAK1 may serve as a potential candidate to relieve neuroinflammatory responses triggered by SAH.

scholarly journals CYP450 Mediates Reactive Oxygen Species Production in a Mouse Model of β-Thalassemia through an Increase in 20-HETE Activity

2021 ◽  
Vol 22 (3) ◽  
pp. 1106
Author(s):  
Rayan Bou-Fakhredin ◽  
Batoul Dia ◽  
Hilda E. Ghadieh ◽  
Stefano Rivella ◽  
Maria Domenica Cappellini ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Mouse Model ◽  
Cell Injury ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Species Production ◽  
Different Sources ◽  
Dependent Pathway

Oxidative damage by reactive oxygen species (ROS) is one of the main contributors to cell injury and tissue damage in thalassemia patients. Recent studies suggest that ROS generation in non-transfusion-dependent (NTDT) patients occurs as a result of iron overload. Among the different sources of ROS, the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes and cytochrome P450 (CYP450) have been proposed to be major contributors for oxidative stress in several diseases. However, the sources of ROS in patients with NTDT remain poorly understood. In this study, Hbbth3/+ mice, a mouse model for β-thalassemia, were used. These mice exhibit an unchanged or decreased expression of the major NOX isoforms, NOX1, NOX2 and NOX4, when compared to their C57BL/6 control littermates. However, a significant increase in the protein synthesis of CYP4A and CYP4F was observed in the Hbbth3/+ mice when compared to the C57BL/6 control mice. These changes were paralleled by an increased production of 20-hydroxyeicosatetraenoic acid (20-HETE), a CYP4A and CYP4F metabolite. Furthermore, these changes corroborate with onset of ROS production concomitant with liver injury. To our knowledge, this is the first report indicating that CYP450 4A and 4F-induced 20-HETE production mediates reactive oxygen species overgeneration in Hbbth3/+ mice through an NADPH-dependent pathway.

scholarly journals Differential involvement of reactive oxygen species in a mouse model of capsaicin-induced secondary mechanical hyperalgesia and allodynia

2017 ◽  
Vol 13 ◽  
pp. 174480691771390 ◽  
Author(s):  
Jun-Ho La ◽  
Jigong Wang ◽  
Alice Bittar ◽  
Hyun Soo Shim ◽  
Chilman Bae ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Mouse Model ◽  
Reactive Oxygen ◽  
Mechanical Hyperalgesia ◽  
Oxygen Species ◽  
Differential Involvement
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