Effect of Arsenite on Induction of CYP1A and CYP2H in Primary Cultures of Chick Hepatocytes

Jacobs, Judith M.; Roussel, Robert R.; Roberts, Maurice; Marek, Doreen; Wood, Sheryl G.; Walton, Heidi S.; Dwyer, Barney E.; Sinclair, Peter R.; Sinclair, Jacqueline F.

doi:10.1006/taap.1998.8436

Cited by 29 publications

(17 citation statements)

References 28 publications

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“…Similar results have been observed when cells were cotreated with PAHs and As 3ϩ (Jacobs et al, 1998(Jacobs et al, , 1999Vakharia et al, 2001;Vernhet et al, 2003). It has been postulated that this inhibition is the result of interference by As 3ϩ with the catalytic potential of CYP1A1, either through reduction in cellular heme pools or by direct binding of As 3ϩ to CYP1A1.…”

Section: Discussionsupporting

confidence: 75%

Arsenite Inhibition of CYP1A1 Induction by 2,3,7,8-Tetrachlorodibenzo-p-dioxin Is Independent of Cell Cycle Arrest

Bonzo

Chen²,

Galijatovic³

et al. 2005

Mol Pharmacol

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We show here that arsenite (As 3ϩ ) elicits multiple effects on gene control, such as the interruption of cell cycle control by initiating G 2 /M arrest as well as inhibiting the aryl hydrocarbon (Ah) receptor-mediated 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible expression of CYP1A1. This raises the question as to whether As 3ϩ is selectively inhibiting TCDD induction of CYP1A1 independent of cell cycle control. As 3ϩ stimulated a concentration-dependent increase in G 2 /M phase arrest that was detected at 12.5 M As 3ϩ . However, cotreatment of HepG2 cells with TCDD and concentrations of As 3ϩ as low as 0.5 M stimulated a pronounced decrease in the induction of CYP1A1-dependent ethoxyresorufin-O-deethylase activity and protein, indicating that the inhibition of CYP1A1 induction by As 3ϩ was considerably more sensitive than As 3ϩ -initiated cell cycle arrest. Low concentrations of As 3ϩ also initiate a dosedependent reduction in TCDD-induced mouse Cyp1a1 as well as human CYP1A1 in primary hepatocytes cultured from transgenic CYP1A1N ϩ/Ϫ mice. Because primary hepatocytes in culture are quiescent, these results indicate that the actions of As 3ϩ on TCDD-initiated induction of CYP1A1 are independent of cell cycle control. As 3ϩ does not impact on Ah receptor function as evaluated by nuclear transport and binding to xenobiotic responsive element sequences, but it does reduce TCDD-induced CYP1A1 mRNA, a property that is concordant with RNA polymerase II association to the gene and the reduction in transcriptional heteronuclear RNA. We conclude from these studies that interruption of CYP1A1-induced transcription by As 3ϩ is not dependent upon cell cycle arrest.

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Section: Discussionsupporting

confidence: 75%

Arsenite Inhibition of CYP1A1 Induction by 2,3,7,8-Tetrachlorodibenzo-p-dioxin Is Independent of Cell Cycle Arrest

Bonzo

Chen²,

Galijatovic³

et al. 2005

Mol Pharmacol

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“…Total hepatic cytochrome levels have also been documented in rats with chemically induced (arsenic species) heme oxygenase (43,44). In contrast, the Sinclair laboratory (45) has shown that, although the levels of specific cytochromes P450 decrease with sodium arsenite induction of HO-1, those effects are not the result of increased heme oxygenase activity. Recent studies have also implicated HO-1 in mediating the anti-inflammatory effects of interleukin-10, indicating that HO-1 may also exert its defensive properties via an as yet unexplored mechanism (46,47).…”

Section: Discussionmentioning

confidence: 99%

Non-heme Induction of Heme Oxygenase-1 Does Not Alter Cellular Iron Metabolism

Sheftel

Kim

Ponka

2007

Journal of Biological Chemistry

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The catabolism of heme is carried out by members of the heme oxygenase (HO) family. The products of heme catabolism by HO-1 are ferrous iron, biliverdin (subsequently converted to bilirubin), and carbon monoxide. In addition to its function in the recycling of hemoglobin iron, this microsomal enzyme has been shown to protect cells in various stress models. Implicit in the reports of HO-1 cytoprotection to date are its effects on the cellular handling of heme/iron. However, the limited amount of uncommitted heme in non-erythroid cells brings to question the source of substrate for this enzyme in non-hemolytic circumstances. In the present study, HO-1 was induced by either sodium arsenite (reactive oxygen species producer) or hemin or overexpressed in the murine macrophage-like cell line, RAW 264.7. Both of the inducers elicited an increase in active HO-1; however, only hemin exposure caused an increase in the synthesis rate of the iron storage protein, ferritin. This effect of hemin was the direct result of the liberation of iron from heme by HO. Cells stably overexpressing HO-1, although protected from oxidative stress, did not display elevated basal ferritin synthesis. However, these cells did exhibit an increase in ferritin synthesis, compared with untransfected controls, in response to hemin treatment, suggesting that heme levels, and not HO-1, limit cellular heme catabolism. Our results suggest that the protection of cells from oxidative insult afforded by HO-1 is not due to the catabolism of significant amounts of cellular heme as thought previously.In the average adult, at equilibrium ϳ2 million red blood cells are being turned over every second. In a day, this process requires about 25 mg of iron (Fe) to be recycled from the hemoglobin of effete erythrocytes. Heme oxygenase 1 (HO-1) 2 is the enzyme responsible for catabolizing the heme from senescent red blood cells to release Fe, as well as equimolar amounts of carbon monoxide (CO) and biliverdin, for its eventual reuse in erythropoiesis. Another noninducible isoform of heme oxygenase with heme catabolic properties similar to HO-1, HO-2 is present in substantial levels primarily in the central nervous system and testes (1, 2). Although the heme-degrading function of HO has been known since the 1960s (3, 4), only recently has it been shown that heme oxygenases may be involved in cytoprotection against cellular stresses (for review see Camara and Soares (5), Abraham and Kappas (6), Otterbein et al. (7), and Ryter et al. (8)). This newer discovery of the potential of these enzymes as a tissue defense mechanism has spawned a flurry of studies by numerous groups who have shown by several different approaches that induction or overexpression of heme oxygenase 1 can protect tissues from various insults, including oxidative stress and immune system attack.The precise mechanism by which HO-1 mediates its protective function remains controversial. Breakdown of heme being the only known reaction catalyzed by the enzyme, extensive research has alleged that one or mo...

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“…Arsenite was shown to decrease 3-methylcholanthrene-mediated induction of CYP1A4 and CYP1A5 mRNA (Jacobs et al, 2000), but not phenobarbital (PB)-mediated induction of CYP2H1 mRNA in primary cultures of chick hepatocytes (Jacobs et al, 1998). In primary cultures of rat hepatocytes, arsenite decreased 3-methylcholanthrene-mediated induction of CYP1A1 mRNA, PBmediated induction of CYP2B1 mRNA, and dexamethasone-mediated induction of CYP3A23 mRNA but had no effect on PB-mediated induction of CYP3A23 mRNA (Jacobs et al, 1999).…”

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confidence: 98%

“…PAHs, including benzo [k]fluoranthene, also inductively enhance levels of CYP1 enzymes, thereby facilitating the production of bioactivated forms of PAHs (Vakharia et al, 2001a,b). Heavy metals, such as arsenite, affect PAH bioactivation pathways (Jacobs et al, 1998(Jacobs et al, , 1999(Jacobs et al, , 2000 and could consequently affect carcinogenic risks associated with bioactivated PAHs. Another selection criterion for benzo [k]fluoranthene as the prototypic PAH for these studies is its high inductive capacity for CYP1A1 and CYP1A2 (Vakharia et al, 2001a,b).…”

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confidence: 99%

“…Induction of CYP1A1 is down-regulated by inflammatory cytokines, heavy metals, such as arsenic (Jacobs et al, 1998(Jacobs et al, , 1999(Jacobs et al, , 2000, and oxidative stress (Morel and Barouki, 1998); however, the mechanisms are not well defined. Arsenite was shown to decrease 3-methylcholanthrene-mediated induction of CYP1A4 and CYP1A5 mRNA (Jacobs et al, 2000), but not phenobarbital (PB)-mediated induction of CYP2H1 mRNA in primary cultures of chick hepatocytes (Jacobs et al, 1998).…”

mentioning

confidence: 99%

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MECHANISMS OF ARSENITE-MEDIATED DECREASES IN BENZO[K]FLUORANTHENE-INDUCED HUMAN CYTOCHROME P4501A1 LEVELS IN HEPG2 CELLS

Bessette¹,

Fasco²,

Pentecost³

et al. 2004

Drug Metab Dispos

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Effect of Arsenite on Induction of CYP1A and CYP2H in Primary Cultures of Chick Hepatocytes

Cited by 29 publications

References 28 publications

Arsenite Inhibition of CYP1A1 Induction by 2,3,7,8-Tetrachlorodibenzo-p-dioxin Is Independent of Cell Cycle Arrest

Arsenite Inhibition of CYP1A1 Induction by 2,3,7,8-Tetrachlorodibenzo-p-dioxin Is Independent of Cell Cycle Arrest

Non-heme Induction of Heme Oxygenase-1 Does Not Alter Cellular Iron Metabolism

MECHANISMS OF ARSENITE-MEDIATED DECREASES IN BENZO[K]FLUORANTHENE-INDUCED HUMAN CYTOCHROME P4501A1 LEVELS IN HEPG2 CELLS

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