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Multidrug resistance gene (mdr1) RNA levels in relation to P-glycoprotein content of leukemic cells from patients with acute leukemia.

We have investigated the effects of peroxisome proliferators on rat liver long-chain acyl-CoA thioesterase activities. Subcellular fractionations of liver homogenates from control, clofibrate- and di(2-ethylhexyl)phthalate-treated rats confirmed earlier studies which demonstrated that peroxisome-pro... Full description

Journal Title: Medical oncology (Northwood London, England), June 1995, Vol.12(2), pp.79-86
Main Author: Albertioni, F
Other Authors: Gruber, A , Areström, I , Vitols, S
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 1357-0560
Link: http://search.proquest.com/docview/77774145/?pq-origsite=primo
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title: Multidrug resistance gene (mdr1) RNA levels in relation to P-glycoprotein content of leukemic cells from patients with acute leukemia.
format: Article
creator:
  • Albertioni, F
  • Gruber, A
  • Areström, I
  • Vitols, S
subjects:
  • ATP-Binding Cassette, Sub-Family B, Member 1–Metabolism
  • Adolescent–Pharmacology
  • Adult–Genetics
  • Aged–Drug Therapy
  • Amino Acid Sequence–Genetics
  • Antibody Specificity–Metabolism
  • Antineoplastic Agents–Drug Therapy
  • Blotting, Western–Genetics
  • Densitometry–Metabolism
  • Drug Resistance, Multiple–Genetics
  • Drug Resistance, Neoplasm–Metabolism
  • Female–Pharmacology
  • Humans–Pharmacology
  • Leukemia, Myeloid, Acute–Pharmacology
  • Male–Pharmacology
  • Middle Aged–Pharmacology
  • Molecular Sequence Data–Pharmacology
  • Nucleic Acid Hybridization–Pharmacology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma–Pharmacology
  • RNA, Neoplasm–Pharmacology
  • Sensitivity and Specificity–Pharmacology
  • Tumor Cells, Cultured–Pharmacology
  • Vincristine–Pharmacology
  • ATP-Binding Cassette, Sub-Family B, Member 1
  • Antineoplastic Agents
  • RNA, Neoplasm
  • Vincristine
ispartof: Medical oncology (Northwood, London, England), June 1995, Vol.12(2), pp.79-86
description: We have investigated the effects of peroxisome proliferators on rat liver long-chain acyl-CoA thioesterase activities. Subcellular fractionations of liver homogenates from control, clofibrate- and di(2-ethylhexyl)phthalate-treated rats confirmed earlier studies which demonstrated that peroxisome-proliferating drugs induce long-chain acyl-CoA thioesterase activity mainly in the mitochondrial and cytosolic fractions. The aim of the present study was to investigate whether the induced activities were due to increases in normally expressed enzymes, or due to induction of novel enzymes. To investigate whether structurally different peroxisome proliferators differentially induced thioesterase activities, we tested the effects of di(2-ethylhexyl)phthalate (a plastisizer) and the hypolipidemic drug clofibrate. For this purpose, we established an analytical size exclusion chromatography method. Chromatography of solubilised mitochondrial matrix proteins showed that the activity in control mitochondria was mainly due to enzymes with molecular masses of about 50 kDa and 35 kDa. The activity in samples prepared from clofibrate- and di(2-ethylhexyl)phthalate-treated rats eluted as proteins of about 40 kDa and 110 kDa. Highly purified peroxisomes contained two peaks of activity, which were not induced, that corresponded to molecular masses of 40 kDa and 80 kDa. The 80-kDa peak was shown to be due to dimerization by addition of glycerol. Chromatography of cytosolic fractions from control rat livers indicated the presence of long-chain acyl-CoA thioesterases with molecular masses of approximately 35 kDa and 125 kDa and a broad peak corresponding to a high-molecular-mass protein. The activity in cytosolic fractions from peroxisome-proliferator-treated rats eluted mainly as peaks corresponding to 40, 110 and 150 kDa. In addition, in the 110-kDa peak, a different degree of induction and different chain-length specificities were caused by clofibrate and di(2-ethylhexyl)phthalate, suggesting that these peroxisome proliferators differentially regulate the cytosolic acyl-CoA thioesterase activities. Western blot analysis showed that enzymes in the 40-kDa peak of the peroxisomal and cytosolic fractions were structurally related, but not identical, to a 40-kDa mitochondrial very-long-chain acyl-CoA thioesterase. Our data show that the increased acyl-CoA thioesterase activities in mitochondria and cytosol were mainly due to induction of acyl-CoA thioesterases which are not, or only
language: eng
source:
identifier: ISSN: 1357-0560
fulltext: fulltext
issn:
  • 13570560
  • 1357-0560
url: Link


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titleMultidrug resistance gene (mdr1) RNA levels in relation to P-glycoprotein content of leukemic cells from patients with acute leukemia.
creatorAlbertioni, F ; Gruber, A ; Areström, I ; Vitols, S
contributorAlbertioni, F (correspondence author) ; Albertioni, F (record owner)
ispartofMedical oncology (Northwood, London, England), June 1995, Vol.12(2), pp.79-86
identifierISSN: 1357-0560
subjectATP-Binding Cassette, Sub-Family B, Member 1–Metabolism ; Adolescent–Pharmacology ; Adult–Genetics ; Aged–Drug Therapy ; Amino Acid Sequence–Genetics ; Antibody Specificity–Metabolism ; Antineoplastic Agents–Drug Therapy ; Blotting, Western–Genetics ; Densitometry–Metabolism ; Drug Resistance, Multiple–Genetics ; Drug Resistance, Neoplasm–Metabolism ; Female–Pharmacology ; Humans–Pharmacology ; Leukemia, Myeloid, Acute–Pharmacology ; Male–Pharmacology ; Middle Aged–Pharmacology ; Molecular Sequence Data–Pharmacology ; Nucleic Acid Hybridization–Pharmacology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma–Pharmacology ; RNA, Neoplasm–Pharmacology ; Sensitivity and Specificity–Pharmacology ; Tumor Cells, Cultured–Pharmacology ; Vincristine–Pharmacology ; ATP-Binding Cassette, Sub-Family B, Member 1 ; Antineoplastic Agents ; RNA, Neoplasm ; Vincristine
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descriptionWe have investigated the effects of peroxisome proliferators on rat liver long-chain acyl-CoA thioesterase activities. Subcellular fractionations of liver homogenates from control, clofibrate- and di(2-ethylhexyl)phthalate-treated rats confirmed earlier studies which demonstrated that peroxisome-proliferating drugs induce long-chain acyl-CoA thioesterase activity mainly in the mitochondrial and cytosolic fractions. The aim of the present study was to investigate whether the induced activities were due to increases in normally expressed enzymes, or due to induction of novel enzymes. To investigate whether structurally different peroxisome proliferators differentially induced thioesterase activities, we tested the effects of di(2-ethylhexyl)phthalate (a plastisizer) and the hypolipidemic drug clofibrate. For this purpose, we established an analytical size exclusion chromatography method. Chromatography of solubilised mitochondrial matrix proteins showed that the activity in control mitochondria was mainly due to enzymes with molecular masses of about 50 kDa and 35 kDa. The activity in samples prepared from clofibrate- and di(2-ethylhexyl)phthalate-treated rats eluted as proteins of about 40 kDa and 110 kDa. Highly purified peroxisomes contained two peaks of activity, which were not induced, that corresponded to molecular masses of 40 kDa and 80 kDa. The 80-kDa peak was shown to be due to dimerization by addition of glycerol. Chromatography of cytosolic fractions from control rat livers indicated the presence of long-chain acyl-CoA thioesterases with molecular masses of approximately 35 kDa and 125 kDa and a broad peak corresponding to a high-molecular-mass protein. The activity in cytosolic fractions from peroxisome-proliferator-treated rats eluted mainly as peaks corresponding to 40, 110 and 150 kDa. In addition, in the 110-kDa peak, a different degree of induction and different chain-length specificities were caused by clofibrate and di(2-ethylhexyl)phthalate, suggesting that these peroxisome proliferators differentially regulate the cytosolic acyl-CoA thioesterase activities. Western blot analysis showed that enzymes in the 40-kDa peak of the peroxisomal and cytosolic fractions were structurally related, but not identical, to a 40-kDa mitochondrial very-long-chain acyl-CoA thioesterase. Our data show that the increased acyl-CoA thioesterase activities in mitochondria and cytosol were mainly due to induction of acyl-CoA thioesterases which are not, or only weakly, expressed under normal conditions.
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8Densitometry–Metabolism
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10Drug Resistance, Neoplasm–Metabolism
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12Humans–Pharmacology
13Leukemia, Myeloid, Acute–Pharmacology
14Male–Pharmacology
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16Molecular Sequence Data–Pharmacology
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25RNA, Neoplasm
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titleMultidrug resistance gene (mdr1) RNA levels in relation to P-glycoprotein content of leukemic cells from patients with acute leukemia.
authorAlbertioni, F ; Gruber, A ; Areström, I ; Vitols, S
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2Adult–Genetics
3Aged–Drug Therapy
4Amino Acid Sequence–Genetics
5Antibody Specificity–Metabolism
6Antineoplastic Agents–Drug Therapy
7Blotting, Western–Genetics
8Densitometry–Metabolism
9Drug Resistance, Multiple–Genetics
10Drug Resistance, Neoplasm–Metabolism
11Female–Pharmacology
12Humans–Pharmacology
13Leukemia, Myeloid, Acute–Pharmacology
14Male–Pharmacology
15Middle Aged–Pharmacology
16Molecular Sequence Data–Pharmacology
17Nucleic Acid Hybridization–Pharmacology
18Precursor Cell Lymphoblastic Leukemia-Lymphoma–Pharmacology
19RNA, Neoplasm–Pharmacology
20Sensitivity and Specificity–Pharmacology
21Tumor Cells, Cultured–Pharmacology
22Vincristine–Pharmacology
23ATP-Binding Cassette, Sub-Family B, Member 1
24Antineoplastic Agents
25RNA, Neoplasm
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