Specific Changes in the Protein Composition of Rat Liver in Response to the Peroxisome Proliferators Ciprofibrate, Wy-14,643 and Di-(2-ethylhexyl)phthalate

Overview

Journal Biochem J

Specialty Biochemistry

Date 1985 May 1

PMID 4004798

Citations 4

Authors

T Watanabe

N D Lalwani

J K Reddy

Affiliations

Soon will be listed here.

Abstract

The hypolipidaemic agents ciprofibrate and Wy-14,643 ([4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid) and the phthalate-ester plasticizer di-(2-ethylhexyl)-phthalate (DEHP), like other peroxisome proliferators, produce a significant hepatomegaly and induce the peroxisomal fatty acid beta-oxidation enzyme system together with profound proliferation of peroxisomes in hepatic parenchymal cells. Changes in the profile of liver proteins in rats following induction of peroxisome proliferation by ciprofibrate, Wy-14,643 and DEHP have been analysed by high-resolution two-dimensional gel electrophoresis. The proteins of whole liver homogenates from normal and peroxisome-proliferator-treated rats were separated by two-dimensional gel electrophoresis using isoelectric focusing for acidic proteins and nonequilibrium pH gradient electrophoresis for basic proteins. In the whole liver homogenates, the quantities of six proteins in acidic gels and six proteins in the basic gels increased following induction of peroxisome proliferation. Peroxisome proliferator administration caused a repression of three acidic proteins in the liver homogenates. By the immunoblot method using polyspecific antiserum against soluble peroxisomal proteins and monospecific antiserum against peroxisome proliferation associated Mr 80000 polypeptide (polypeptide PPA-80), the majority of basic proteins induced by these peroxisome proliferators appeared to be peroxisomal proteins. Polypeptide PPA-80 becomes the most abundant protein in the total liver homogenates of peroxisome-proliferator-treated rats. These results indicate that ciprofibrate, DEHP and Wy-14,643 induce marked changes in the profile of specific hepatic proteins and that some of these changes should serve as a baseline to identify a set of gene products that may assist in defining the specific 'peroxisome proliferator domain'.

Citing Articles

Peroxisome proliferators and peroxisome proliferator-activated receptor alpha: biotic and xenobiotic sensing.

Reddy J Am J Pathol. 2004; 164(6):2305-21.

PMID: 15161663 PMC: 1615758. DOI: 10.1016/s0002-9440(10)63787-x.

Identification of novel peroxisome proliferator-activated receptor alpha (PPARalpha) target genes in mouse liver using cDNA microarray analysis.

Cherkaoui-Malki M, Meyer K, Cao W, Latruffe N, Yeldandi A, Rao M Gene Expr. 2002; 9(6):291-304.

PMID: 11764000 PMC: 5964950. DOI: 10.3727/000000001783992533.

Studies on fatty acid-binding proteins. The diurnal variation shown by rat liver fatty acid-binding protein.

WILKINSON T, Wilton D Biochem J. 1987; 242(3):913-7.

PMID: 3593284 PMC: 1147795. DOI: 10.1042/bj2420913.

Functions of fatty acid binding proteins.

Kaikaus R, Bass N, Ockner R Experientia. 1990; 46(6):617-30.

PMID: 2193826 DOI: 10.1007/BF01939701.

References

Baudhuin P, BEAUFAY H, RAHMAN-LI Y, Sellinger O, WATTIAUX R, Jacques P . Tissue fractionation studies. 17. Intracellular distribution of monoamine oxidase, aspartate aminotransferase, alanine aminotransferase, D-amino acid oxidase and catalase in rat-liver tissue. Biochem J. 1964; 92(1):179-84. PMC: 1215456. DOI: 10.1042/bj0920179. View

BEST M, Duncan C . HYPOLIPEMIA AND HEPATOMEGALY FROM ETHYL CHLOROPHENOXYISOBUTYRATE (CPIB) IN THE RAT. J Lab Clin Med. 1964; 64:634-42. View

Svoboda D, GRADY H, Azarnoff D . Microbodies in experimentally altered cells. J Cell Biol. 1967; 35(1):127-52. PMC: 2107117. DOI: 10.1083/jcb.35.1.127. View

Kurup C, Aithal H, Ramasarma T . Increase of hepatic mitochondria on administration of ethyl alpha-p-chlorophenoxyisobutyrate to the rat. Biochem J. 1970; 116(5):773-9. PMC: 1185498. DOI: 10.1042/bj1160773. View

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

Solberg H, Aas M, Daae L . The activity of the different carnitine acyltransferases in the liver of clofibrate-fed rats. Biochim Biophys Acta. 1972; 280(3):434-9. DOI: 10.1016/0005-2760(72)90249-4. View

Gear A, Albert A, Bednarek J . The effect of the hypocholesterolemic drug clofibrate on liver mitochondrial biogenesis. A role for neutral mitochondrial proteases. J Biol Chem. 1974; 249(20):6495-504. View

Moody D, Reddy J . Increase in hepatic carnitine acetyltransferase activity associated with peroxisomal (microbody) proliferation induced by the hypolipidemic drugs clofibrate, nafenopin, and methyl clofenapate. Res Commun Chem Pathol Pharmacol. 1974; 9(3):501-10. View

Ofarrell P . High resolution two-dimensional electrophoresis of proteins. J Biol Chem. 1975; 250(10):4007-21. PMC: 2874754. View

10.

Duve C . Exploring cells with a centrifuge. Science. 1975; 189(4198):186-94. DOI: 10.1126/science.1138375. View

11.

SCHEELE G . Two-dimensional gel analysis of soluble proteins. Charaterization of guinea pig exocrine pancreatic proteins. J Biol Chem. 1975; 250(14):5375-85. View

12.

Reddy J, Krishnakantha T . Hepatic peroxisome proliferation: induction by two novel compounds structurally unrelated to clofibrate. Science. 1975; 190(4216):787-9. DOI: 10.1126/science.1198095. View

13.

Lazarow P, DE DUVE C . A fatty acyl-CoA oxidizing system in rat liver peroxisomes; enhancement by clofibrate, a hypolipidemic drug. Proc Natl Acad Sci U S A. 1976; 73(6):2043-6. PMC: 430444. DOI: 10.1073/pnas.73.6.2043. View

14.

Moody D, Reddy J . Morphometric analysis of the ultrastructural changes in rat liver induced by the peroxisome proliferator SaH 42-348. J Cell Biol. 1976; 71(3):768-80. PMC: 2109794. DOI: 10.1083/jcb.71.3.768. View

15.

Reddy J, Kumar N . The peroxisome proliferation-associated polypeptide in rat liver. Biochem Biophys Res Commun. 1977; 77(3):824-9. DOI: 10.1016/s0006-291x(77)80052-1. View

16.

OFarrell P, Goodman H, Ofarrell P . High resolution two-dimensional electrophoresis of basic as well as acidic proteins. Cell. 1977; 12(4):1133-41. DOI: 10.1016/0092-8674(77)90176-3. View

17.

Ivarie R, Ofarrell P . The glucocorticoid domain: steroid-mediated changes in the rate of synthesis of rat hepatoma proteins. Cell. 1978; 13(1):41-55. DOI: 10.1016/0092-8674(78)90136-8. View

18.

Moody D, Reddy J . The hepatic effects of hypolipidemic drugs (clofibrate, nafenopin, tibric acid, and Wy-14,643) on hepatic peroxisomes and peroxisome-associated enzymes. Am J Pathol. 1978; 90(2):435-46. PMC: 2018144. View

19.

Lazarow P . Rat liver peroxisomes catalyze the beta oxidation of fatty acids. J Biol Chem. 1978; 253(5):1522-8. View

20.

Reddy J, Kumar N . Stimulation of catalase synthesis and increase of carnitine acetyltransferase activity in the liver of intact female rats fed clofibrate. J Biochem. 1979; 85(3):847-56. View