Aquaporin-4 knockout enhances astrocyte toxicity induced by 1-methyl-4-phenylpyridinium ion and lipopolysaccharide via increasing the expression of cytochrome P4502E1

Hao, Chunshu; Liu, Wei; Luan, Xiaofei; Yang, Li; Gui, Haiyan; Peng, Yan; Shen, Jian‐Yong; Hu, Gang; Yang, Jian

doi:10.1016/j.toxlet.2010.06.023

Cited by 16 publications

(22 citation statements)

References 28 publications

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“…For example, the early induction of AQP4 by a low dose of thrombin contributes to limitation of the ischemic infarction and formation of edema in mice [48] , and acute vascular disruption is associated with AQP4 loss after transient MCAO in rats [49] . This protective role is also reported in spinal cord compression injury [50] , subarachnoid hemorrhage [51] , intracerebral hemorrhage [52] and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity [53,54] . These findings demonstrate that AQP4 in astrocytes exerts a beneficial action in pathological conditions.…”

Section: Discussionsupporting

confidence: 56%

Aggravated inflammation and increased expression of cysteinyl leukotriene receptors in the brain after focal cerebral ischemia in AQP4-deficient mice

Shi

Zhao

et al. 2012

Neurosci. Bull.

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Objective Aquaporin-4 (AQP4), the main water channel protein in the brain, plays a critical role in water homeostasis and brain edema. Here, we investigated its role in the inflammatory responses after focal cerebral ischemia. MethodsIn AQP4-knockout (KO) and wild-type mice, focal cerebral ischemia was induced by 30 min of middle cerebral arterial occlusion (MCAO). Ischemic neuronal injury and cellular inflammatory responses, as well as the expression and localization of cysteinyl leukotriene CysLT 2 and CysLT 1 receptors, were determined at 24 and 72 h after MCAO.Results AQP4-KO mice showed more neuronal loss, more severe microglial activation and neutrophil infiltration, but less astrocyte proliferation in the brain after MCAO than wild-type mice. In addition, the protein levels of both CysLT 1 and CysLT 2 receptors were up-regulated in the ischemic brain, and the up-regulation was more pronounced in AQP4-KO mice. The CysLT 1 and CysLT 2 receptors were primarily localized in neurons, microglia and neutrophils; those localized in microglia and neutrophils were enhanced in AQP4-KO mice. Conclusion AQP4 may play an inhibitory role in postischemic inflammation.

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Section: Discussionsupporting

confidence: 56%

Aggravated inflammation and increased expression of cysteinyl leukotriene receptors in the brain after focal cerebral ischemia in AQP4-deficient mice

Shi

Zhao

et al. 2012

Neurosci. Bull.

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“…These data are consistent with earlier findings (Upadhya et al, 2000, Hao et al, 2010) where CYP2E1 was found in GFAP + cells and, occasionally, in vessels. After severe status epilepticus (SE), CYP2E1 immunoreactivity was regionally increased in CA2/3 and hilar but not in CA1 hippocampal neurons (Figure 1A).…”

Section: Resultssupporting

confidence: 94%

“…The presented data and available evidences (Tindberg et al, 1996, Upadhya et al, 2001, Pardini et al, 2008, Hao et al, 2010, Mann et al, 2012, Zhong et al, 2012, Birnie et al, 2013) support the hypothesis of drug biotransformation in healthy and diseased brain ( e.g ., traumatic brain injury, ischemia, Alzheimer’s’ disease, epilepsy). Further studies are required to fully elucidate the functional relevance of selected P450 enzymes, such as CYP2E1, in the epileptic brain.…”

Section: Resultssupporting

confidence: 74%

“…For instance, CYP2E1 was proposed as a mechanism of free radical production by brain endothelial cells after exposure to ethanol (Haorah et al, 2005). A link between astrocytic aquaporin-4, decreased CYP2E1 and protection to reactive oxygen species was recently proposed (Hao et al, 2010). Reactive oxygen species induced by ethanol parallel CYP2E1 over-expression in the hippocampus and cell damage, suggesting that CYP2E1 mediates the toxic effects of ethanol on neurons (Zhong et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

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Effect of status epilepticus and antiepileptic drugs on CYP2E1 brain expression

et al. 2014

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P450 metabolic enzymes are expressed in the human and rodent brain. Recent data support their involvement in the pathophysiology of epilepsy. However, the determinants of metabolic enzyme expression in the epileptic brain are unclear. We tested the hypothesis that status epilepticus or exposure to phenytoin or phenobarbital affects brain expression of the metabolic enzyme CYP2E1. Status epilepticus (SE) was induced in C57BL/6J mice by systemic kainic acid. Brain CYP2E1 expression was evaluated 18–24 hours after SE by immunohistochemistry. Co-localization with NEUN, GFAP and CD31 was determined by confocal microscopy. The effect of phenytoin, carbamazepine and phenobarbital on CYP2E1 expression was evaluated in vivo or by using organotypic hippocampal cultures in vitro. CYP2E1 expression was investigated in brain resections from a cohort of drug resistant epileptic brain resections and human endothelial cultures (EPI-EC). Immunohistochemistry showed an increase of CYP2E1 expression limited to hippocampal CA2/3 and hilar neurons after severe SE in mice. CYP2E1 expression was also observed at the astrocyte-vascular interface. Analysis of human brain specimens revealed CYP2E1 expression in neurons and vascular endothelial cells (EC). CYP2E1 was expressed in cultured human EC and over-expressed by EPI-EC. When analyzing the effect of drug exposure on CYP2E1 expression we found that, in vivo or in vitro, ethanol increased CYP2E1 levels in the brain and liver. Treatment with phenytoin induced localized CYP2E1 expression in the brain whereas no significant effects were exerted by carbamazepine or phenobarbital. Our data indicate that the effect of acute SE on brain CYP2E1 expression is localized and cell specific. Exposure to selected anti-epileptic drugs could play a role in determining CYP2E1 brain expression. Additional investigation is required to fully reproduce the culprits of P450 enzyme expression as observed in the human epileptic brain.

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“…CYP2E1 inhibitors protect the cell from damage and the production of ROS induced by 1-methyl-4-phenylpyridinium ions (MPP + ), LPS, and ethanol in wild-type primary astrocytes [82]. …”

Section: Protein Mrna and Activity Modulation Of Cyp2e1 In The Bmentioning

confidence: 99%

The Role of CYP2E1 in the Drug Metabolism or Bioactivation in the Brain

García-Suástegui

Ramos-Chávez

Rubio-Osornio

et al. 2017

Oxidative Medicine and Cellular Longevity

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Organisms have metabolic pathways that are responsible for removing toxic agents. We always associate the liver as the major organ responsible for detoxification of the body; however this process occurs in many tissues. In the same way, as in the liver, the brain expresses metabolic pathways associated with the elimination of xenobiotics. Besides the detoxifying role of CYP2E1 for compounds such as electrophilic agents, reactive oxygen species, free radical products, and the bioactivation of xenobiotics, CYP2E1 is also related in several diseases and pathophysiological conditions. In this review, we describe the presence of phase I monooxygenase CYP2E1 in regions of the brain. We also explore the conditions where protein, mRNA, and the activity of CYP2E1 are induced. Finally, we describe the relation of CYP2E1 in brain disorders, including the behavioral relations for alcohol consumption via CYP2E1 metabolism.

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Aquaporin-4 knockout enhances astrocyte toxicity induced by 1-methyl-4-phenylpyridinium ion and lipopolysaccharide via increasing the expression of cytochrome P4502E1

Cited by 16 publications

References 28 publications

Aggravated inflammation and increased expression of cysteinyl leukotriene receptors in the brain after focal cerebral ischemia in AQP4-deficient mice

Aggravated inflammation and increased expression of cysteinyl leukotriene receptors in the brain after focal cerebral ischemia in AQP4-deficient mice

Effect of status epilepticus and antiepileptic drugs on CYP2E1 brain expression

The Role of CYP2E1 in the Drug Metabolism or Bioactivation in the Brain

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