Peroxisome proliferation in primary cultures of rat hepatocytes

Gray, Tim J.B.; Lake, Brian G.; Beamand, J.A.; Foster, John R.; Gangolli, S.D.

doi:10.1016/0041-008x(83)90240-5

Cited by 178 publications

(47 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One of the potent peroxisome proliferators is WY-14,643, a hypolipidemic drug, that has been extensively characterized as a non-genotoxic rodent hepatocarcinogen (Reddy et al, 1979). WY-14,643 is also known to be a PPAR agonist (Gray et al, 1983). …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Peroxisome proliferator-activated receptor .ALPHA. (PPAR.ALPHA.) agonist, WY-14,643, increased transcription of myosin light chain-2 in cardiomyocytes.

et al. 2001

View full text Add to dashboard Cite

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that can be activated by xenobiotics and natural fatty acids. To assess the potential physiological activity of PPAR ligands on cardiac muscular cells, the effects of PPAR agonist, WY-14,643, on both rat hearts and a rat cardiomyocyte cell line (H9c2 cells) were investigated. Male F344 rats were fed a diet containing WY-14,643 at a concentration of 100 ppm for 26 weeks. Cardiac muscular hypertrophy was revealed by morphometric analysis in which the diameter of the muscular fibers in WY-14,643-treated rats was larger than those of control rats. Using H9c2 cells in vitro, the protein content per cell was increased in a dosedependent manner with the treatment of WY-14,643. The transcription of myosin light chain-2 (MLC-2), a parameter of myocardial hypertrophy, was increased in H9c2 cells transfected with the rat MLC-2/luciferase fusion gene by WY-14,643 as well as other peroxisome proliferators, clofibrate and di(2-ethylhexyl) phthalate. In addition, accumulation of myosin light chain protein was confirmed in H9c2 cells treated with WY-14,643 at 10 g/ml for 7 days or more by immunohistochemistry. These results suggest that PPAR ligands have a potential to regulate MLC-2, which is a contractile protein in cardiomyocytes and may play a part of role in the pathogenesis of cardiac hypertrophy.

show abstract

Section: Discussionmentioning

confidence: 99%

“…WY-14,643 is a well-known strong peroxisome proliferator and PPAR agonist (Gray et al, 1983). It increases peroxisomes in hepatocytes and induces liver tumors in rodents (Reddy et al, 1979).…”

Section: Introductionmentioning

confidence: 99%

Peroxisome proliferator-activated receptor .ALPHA. (PPAR.ALPHA.) agonist, WY-14,643, increased transcription of myosin light chain-2 in cardiomyocytes.

et al. 2001

View full text Add to dashboard Cite

show abstract

“…Their purity was established by thin layer chromatography, nuclear magnetic resonance spectroscopy and by elemental analysis. DEHP (99.5% pure) was the generous gift of BP Chemicals Ltd., Sully, South Glamorgan, Wales, U.K. All other peroxisome proliferators, enzyme substrates and cofactors and tissue culture materials were obtained from the sources cited previously (14)(15)(16)(17).…”

Section: Methodsmentioning

confidence: 99%

“…Hepatocyte whole homogenate and/or liver whole homogenate fractions were assayed for activities of KCNinsensitive palmitoyl-CoA oxidation, carnitine acetyltransferase, total and heat labile enoyl-CoA hydratase, and protein content as described previously (14)(15)(16). The activity of lauric acid hydroxylation (measured as the combined 11-and 12-hydroxylation) in hepatocyte whole homogenates was measured by the method of Lake et al (18).…”

Section: Biochemical Determinationsmentioning

confidence: 99%

Hepatic Effects of Phthalate Esters and Related Compounds. In Vivo and In Vitro Correlations

Lake¹,

Gray²,

Gangolli³

1986

Environmental Health Perspectives

Self Cite

View full text Add to dashboard Cite

The hepatic effects of phthalate esters and related compounds on peroxisomal and microsomal enzyme activities were investigated in the intact animal and in primary hepatocyte cultures. In vitro studies with a series of phthalate monoesters demonstrated structure activity differences in the induction of the specific peroxisomal marker KCN-insensitive palmitoyl-CoA oxidation and also of carnitine acetyltransferase. These effects could be reproduced in vivo, and potency differences were also observed between di(2-ethylhexyl) phthalate (DEHP) and its straight-chain isomer, di-n-octyl phthalate. In in vivo studies, DEHP, mono(2-ethylhexyl) phthalate, and clofibrate/clofibric acid produced large increases in liver size and peroxisomal enzyme activities in Sprague-Dawley rats and Chinese hamsters, but had less effect in Syrian hamsters. These effects could be largely reproduced in vitro where good responses were obtained with rat and Chinese hamster hepatocytes, but either little or no effect with Syrian hamster and DunkinHartley guinea pig hepatocytes. Both DEHP and clofibrate appeared to induce similar form(s) of microsomal cytochrome P-450 which exhibited a high specificity towards lauric acid hydroxylation. With a range of hypolipidemic agents, including phthalate monoesters, a good correlation was observed between the induction of peroxisomal and microsomal enzyme activities in rat hepatocyte cultures. These results thus demonstrate a good relationship between the in vivo and in vitro effects of phthalate esters and related compounds and suggest that hepatocyte cultures may be useful for further studies on the hepatic effects of peroxisome proliferators.

show abstract

“…These esters are widely distributed throughout the environment and also have been detected in animals and humans [12,23]. Short-term administration of di(2-ethylhexyl)phthalate (DEHP) to rats causes liver enlargement with a marked proliferation of peroxisomes [6,7,9]. To clarify the mechanism of toxicity of PhEs in rats, we have already investigated the administration of PhEs such as DBP [21] and DEHP [3] which disturbed the metabolism of de novo NAD biosynthesis.…”

Section: Introductionmentioning

confidence: 99%

Effects of Dietary Di(2-ethylhexyl)phthalate on the Metabolism of Tryptophan to Niacin in Mice

et al. 2004

View full text Add to dashboard Cite

Abstract:We have reported the effect of di(2-ethylhexyl)phthalate (DEHP) on the tryptophan (Trp)-niacin pathway in rats. To clarify the universal effect of DEHP on rodents, we studied whether DEHP also has an effect on Trp metabolism in mice. Mice were fed a niacin-free, 20% casein diet supplemented with DEHP for 21 days. Feeding with DEHP decreased the body weight gain and increased the liver weight in correlation with the dose level of DEHP. The administration of DEHP significantly increased the formation of quinolinic acid and the lower metabolites of the Trp-niacin pathway. The flux of niacin in the lower part of the Trp-niacin pathway in mice was enhanced by feeding with DEHP. Key words: niacin, phthalate esters, tryptophan lower metabolites were increased by feeding rats a diet containing DEHP [4]. However, there are no reports on the effect of DEHP on Trp to niacin metabolism in the mouse. To further clarify the universal effect of DEHP on rodents, we investigated whether DEHP also has an effect on Trp metabolism in mice.Vitamin-free milk casein, sucrose, L-methionine, nicotinamide (Nam), and anthranilic acid (AnA) were purchased from Wako Pure Chemical Industries (Osaka Japan). Kynurenine sulfate, kynurenic acid (KA), 3-hydroxyanthranilic acid (3-HA), and N 1 -methylnicotinamide (MNA) chloride were purchased from Tokyo Kasei Kogyo (Tokyo, Japan). Phthalic acid esters (PhEs), which are known to cause tetany of fish, and malformation of the mouse fetus, are used in a variety of industrial applications and they are constituents of diverse products such as paints, adhesives, cosmetics and polyvinylchloride plastics [10]. These esters are widely distributed throughout the environment and also have been detected in animals and humans [12,23]. Short-term administration of di(2-ethylhexyl)phthalate (DEHP) to rats causes liver enlargement with a marked proliferation of peroxisomes [6,7,9]. To clarify the mechanism of toxicity of PhEs in rats, we have already investigated the administration of PhEs such as DBP [21] and DEHP [3] which disturbed the metabolism of de novo NAD biosynthesis. The formation of the key metabolite of tryptophan (Trp) to the niacin pathway, quinolinic acid (QA), and its

show abstract

Peroxisome proliferation in primary cultures of rat hepatocytes

Cited by 178 publications

References 29 publications

Peroxisome proliferator-activated receptor .ALPHA. (PPAR.ALPHA.) agonist, WY-14,643, increased transcription of myosin light chain-2 in cardiomyocytes.

Peroxisome proliferator-activated receptor .ALPHA. (PPAR.ALPHA.) agonist, WY-14,643, increased transcription of myosin light chain-2 in cardiomyocytes.

Hepatic Effects of Phthalate Esters and Related Compounds. In Vivo and In Vitro Correlations

Effects of Dietary Di(2-ethylhexyl)phthalate on the Metabolism of Tryptophan to Niacin in Mice

Contact Info

Product

Resources

About