Expression of multiple forms of brain cytochrome P450

Strobel, Henry W.; Kawashima, Hidenori; Geng, Jie; Sequeira, David J.; Bergh, A F; Hodgson, Anne V.; Wang, Huamin; Shen, Sijiu

doi:10.1016/0378-4274(95)03509-5

Cited by 31 publications

(8 citation statements)

References 11 publications

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“…Several of the CYP isoforms have been shown to be expressed in the brain, which exhibit highly regional and cellular specificity (Anandatheerthavarada et al, 1990;Ghersi-Egea et al, 1994;Miksys and Tyndale, 2002;Parmar et al, 2003;Ravindranath et al, 1995;Strobel et al, 1995). Although the CYP content in brain is too low (1-5% of liver enzymes) to influence the overall pharmacokinetics of the xenobiotics, bioactivation of xenobiotics within the brain is of significance as the polar metabolites formed by the CYPs cannot cross the blood brain barrier and could damage tissue macromolecules (Miksys and Tyndale, 2002;Parmar et al, 2003;Strobel et al, 1995). Considering the limited regenerative capacity of the brain, such damages could result in serious consequences including lifetime defects.…”

Section: Introductionmentioning

confidence: 97%

Differences in sensitivity of cultured rat brain neuronal and glial cytochrome P450 2E1 to ethanol

et al. 2006

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Section: Introductionmentioning

confidence: 97%

Differences in sensitivity of cultured rat brain neuronal and glial cytochrome P450 2E1 to ethanol

et al. 2006

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“…In addition, it has been shown that cytochrome P450 in the brain may have homeostatic functions because isoforms have been shown to participate in cerebral blood vessel tone and also in the synthesis of neuroactive steroids (Walther et al, 1987;Warner et al, 1994;Harder et al, 1997). Current evidence shows that CYP1A1/2, CYP2B1, CYP2E1, CYP2D1, novel forms from the CYP3A and CYP4F families, and CYP7B exist in the brain and are regionally located in both neuronal and glial cells (Strobel et al, 1995;Miksys et al, 2000).…”

mentioning

confidence: 99%

The Role of Cytokines in the Depression of CYP1A Activity Using Cultured Astrocytes as an in Vitro Model of Inflammation in the Central Nervous System

Nicholson

Renton²

2002

Drug Metab Dispos

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This paper is available online at http://dmd.aspetjournals.org ABSTRACT:The interaction and modulation of hepatic cytochrome P450 enzymes by infection and inflammation has been well described both in clinical settings and in animal models. Recent evidence found that inflammation in the central nervous system (CNS) leads to alterations in cytochrome P450 activity in both brain and liver. The bacterial endotoxin lipopolysaccharide (LPS) was used to induce an inflammatory response in cultured astrocytes as a model of CNS inflammation. This inflammatory response involves a range of immune mediators, such as acute phase cytokines, nitric oxide, prostanoid products, and reactive oxygen species. It is hypothesized that cytokines, released during inflammation, act to modulate the expression of specific isoforms of cytochrome P450 resulting in altered activity levels. High levels of the cytokines tumor necrosis factor-␣ and interleukin-1␤ were released into culture medium after the addition of LPS to astrocyte cultures. When these same cytokines were added directly to the cultures, they also were able to modulate levels of CYP1A activity. The concurrent addition of dexamethasone to astrocytes blocked both the cytokine release and the alteration of CYP1A activity, thus supporting a role for these cytokines in this response. These results provide evidence suggesting an involvement of acute phase cytokines in mediating the LPS-induced depression of CYP1A activity in cultured astrocytes.

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“…These differences in the induction of P450 enzymes could be attributed to the differences in the amounts of P450 isoenzymes expressed in these brain regions and their relative sensitivity towards deltamethrin (Anandatheerthavarada et al, 1990;Strobel et al 1995;Parmar et al, 1998;Tirumalai et al 1998). Previous studies from our laboratory have also shown significant difference amongst the different brain regions to dealkylate ER and PR indicating differences in the presence of varying amounts of P450s in different brain regions .…”

Section: Discussionmentioning

confidence: 70%

Induction of rat brain cytochrome P450s (P450s) by deltamethrin: Regional specificity and correlation with neurobehavioral toxicity

et al. 2001

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Oral administration of 5 mg/kg body weight of deltamethrin, an alpha-cyano type II pyrethroid insecticide once a day for 1, 7, 15 and 21 consecutive days to young Druckerey rats (6- 8 weeks old) produced a time dependent increase in the activity of cytochrome P450 (P450) dependent 7-ethoxyresorufin-O-deethylase (EROD) and 7-pentoxyresorufin-O-dealkylase (PROD) in rat brain microsomes. A significant induction was observed on prolonged exposure of deltamethrin for 15 or 21 days. The induction in the activity of cerebral P450 enzymes was associated with the time dependent increase in the spontaneous locomotor activity indicating accumulation of deltamethrin or its metabolites in brain with the increase in the duration of exposure. Administration of deltamethrin (5 mg/kg) for 21 days produced region specific changes in the dealkylation of ethoxyresorufin and pentoxyresorufin in rat brain with significant induction occurring in the activity of P450 1A1/2 dependent EROD in cerebellum, hippocampus, hypothalamus and medulla-pons and that of P450 2B1/2 mediated PROD in hippocampus, hypothalamus, corpus striatum and mid brain. The data suggests that the differences in the induction of individual P450 isoenzymes in diverse brain regions could play a role in regulating the response of brain to pyrethroid insecticides by modulating their concentration per se or their active metabolites at the target site(s).

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Expression of multiple forms of brain cytochrome P450

Cited by 31 publications

References 11 publications

Differences in sensitivity of cultured rat brain neuronal and glial cytochrome P450 2E1 to ethanol

Differences in sensitivity of cultured rat brain neuronal and glial cytochrome P450 2E1 to ethanol

The Role of Cytokines in the Depression of CYP1A Activity Using Cultured Astrocytes as an in Vitro Model of Inflammation in the Central Nervous System

Induction of rat brain cytochrome P450s (P450s) by deltamethrin: Regional specificity and correlation with neurobehavioral toxicity

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