Effect of thyroid hormones on the modulation of genetic expression of liver cytosolic malic enzyme, in rats poisoned with hexachlorobenzene
Hexachlorobenzene (HCB) is a widespread environmental pollutant. Chronic exposure of laboratory animals to HCB triggers porphyria, induction of liver microsomal enzymes, low levels of T4 reproductive dysfunction's, liver and thyroid tumors. Previous findings from our laboratory have shown that...
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1998
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03276309_v48_n3_p125_LoaizaPerez http://hdl.handle.net/20.500.12110/paper_03276309_v48_n3_p125_LoaizaPerez |
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paper:paper_03276309_v48_n3_p125_LoaizaPerez2023-06-08T15:33:27Z Effect of thyroid hormones on the modulation of genetic expression of liver cytosolic malic enzyme, in rats poisoned with hexachlorobenzene Loaiza Pérez, Andrea Irene Sancovich, Horacio Alberto Kleiman de Pisarev, Diana L. Randi, Andrea Silvana Ferramola, Ana María fungicide glyceraldehyde 3 phosphate dehydrogenase glycerol 3 phosphate dehydrogenase hexachlorobenzene liothyronine messenger RNA phosphoenolpyruvate carboxylase thyroid hormone receptor thyroxine animal article cytosol drug effect enzymology female gene expression regulation genetics liver liver mitochondrion metabolism physiology rat time Wistar rat Animals Cytosol Female Fungicides, Industrial Gene Expression Regulation, Enzymologic Glyceraldehyde-3-Phosphate Dehydrogenases Glycerolphosphate Dehydrogenase Hexachlorobenzene Liver Mitochondria, Liver Phosphoenolpyruvate Carboxylase Rats Rats, Wistar Receptors, Thyroid Hormone RNA, Messenger Thyroxine Time Factors Triiodothyronine Hexachlorobenzene (HCB) is a widespread environmental pollutant. Chronic exposure of laboratory animals to HCB triggers porphyria, induction of liver microsomal enzymes, low levels of T4 reproductive dysfunction's, liver and thyroid tumors. Previous findings from our laboratory have shown that HCB increased the activity of the liver thyroid-responsive enzymes: malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PD) without any change in the mytochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD). In this study we have demonstrated that HCB treatment increased ME mRNA. We also have investigated if HCB affected: a) the thyroid hormone receptor (TR) concentration and binding affinity for its ligands, b) specifically the ME gene expression, or other thyroid hormone responsive enzymes were affected as well, c) Protein/DNA complex formed on the thyroid responsive element (TRE). Livers from female Wistar rats intoxicated with HCB (100 mg/100 g b.w.), for 9 and 15 days, were analyzed. Northern blot hybridization analysis, have demonstrated that ME mRNA levels increased 4 times and 2 times after 9 and 15 days intoxication respectively, without any alterations in the mRNA levels of other thyroid hormone responsive enzymes such as glyceraldheyde 3- phosphate dehydrogenase, phosphoenolpyruvatecarboxikinase and alpha-GPD. These results suggest that HCB affects specifically, ME gene expression. Hepatic T3 and T4 levels evaluated by RIA were not affected by HCB. Scatchard analyses showed that TR affinity and number of sites were not altered after 9 and 15 days of HCB treatment (control, Ka: 1.9 nM, Bmax 3.9 f/mol 100 micrograms DNA: HCD 9 days Ka: 2.1 nM, Bmax 4.5 fmol/100 micrograms DNA: HCB 15 days Ka 1.9 nM. Bmax 5.1 fmol/100 micrograms DNA intoxication, neither at 9 nor at 15 days. Electrophoresis mobility shift assay showed that HCB did not modify nuclear protein extract affinity for the TREs sequence. Our results suggest that TR itself was not directly involved in the induction of ME gene expression by HCB. Nevertheless TR could interact with other transcription factors in the overexpression of ME gene. Fil:Loaiza Perez, A.I. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Sancovich, H.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Kleiman De Pisarev, D.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Randi, A.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Ferramola De Sancovich, A.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 1998 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03276309_v48_n3_p125_LoaizaPerez http://hdl.handle.net/20.500.12110/paper_03276309_v48_n3_p125_LoaizaPerez |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
fungicide glyceraldehyde 3 phosphate dehydrogenase glycerol 3 phosphate dehydrogenase hexachlorobenzene liothyronine messenger RNA phosphoenolpyruvate carboxylase thyroid hormone receptor thyroxine animal article cytosol drug effect enzymology female gene expression regulation genetics liver liver mitochondrion metabolism physiology rat time Wistar rat Animals Cytosol Female Fungicides, Industrial Gene Expression Regulation, Enzymologic Glyceraldehyde-3-Phosphate Dehydrogenases Glycerolphosphate Dehydrogenase Hexachlorobenzene Liver Mitochondria, Liver Phosphoenolpyruvate Carboxylase Rats Rats, Wistar Receptors, Thyroid Hormone RNA, Messenger Thyroxine Time Factors Triiodothyronine |
| spellingShingle |
fungicide glyceraldehyde 3 phosphate dehydrogenase glycerol 3 phosphate dehydrogenase hexachlorobenzene liothyronine messenger RNA phosphoenolpyruvate carboxylase thyroid hormone receptor thyroxine animal article cytosol drug effect enzymology female gene expression regulation genetics liver liver mitochondrion metabolism physiology rat time Wistar rat Animals Cytosol Female Fungicides, Industrial Gene Expression Regulation, Enzymologic Glyceraldehyde-3-Phosphate Dehydrogenases Glycerolphosphate Dehydrogenase Hexachlorobenzene Liver Mitochondria, Liver Phosphoenolpyruvate Carboxylase Rats Rats, Wistar Receptors, Thyroid Hormone RNA, Messenger Thyroxine Time Factors Triiodothyronine Loaiza Pérez, Andrea Irene Sancovich, Horacio Alberto Kleiman de Pisarev, Diana L. Randi, Andrea Silvana Ferramola, Ana María Effect of thyroid hormones on the modulation of genetic expression of liver cytosolic malic enzyme, in rats poisoned with hexachlorobenzene |
| topic_facet |
fungicide glyceraldehyde 3 phosphate dehydrogenase glycerol 3 phosphate dehydrogenase hexachlorobenzene liothyronine messenger RNA phosphoenolpyruvate carboxylase thyroid hormone receptor thyroxine animal article cytosol drug effect enzymology female gene expression regulation genetics liver liver mitochondrion metabolism physiology rat time Wistar rat Animals Cytosol Female Fungicides, Industrial Gene Expression Regulation, Enzymologic Glyceraldehyde-3-Phosphate Dehydrogenases Glycerolphosphate Dehydrogenase Hexachlorobenzene Liver Mitochondria, Liver Phosphoenolpyruvate Carboxylase Rats Rats, Wistar Receptors, Thyroid Hormone RNA, Messenger Thyroxine Time Factors Triiodothyronine |
| description |
Hexachlorobenzene (HCB) is a widespread environmental pollutant. Chronic exposure of laboratory animals to HCB triggers porphyria, induction of liver microsomal enzymes, low levels of T4 reproductive dysfunction's, liver and thyroid tumors. Previous findings from our laboratory have shown that HCB increased the activity of the liver thyroid-responsive enzymes: malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PD) without any change in the mytochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD). In this study we have demonstrated that HCB treatment increased ME mRNA. We also have investigated if HCB affected: a) the thyroid hormone receptor (TR) concentration and binding affinity for its ligands, b) specifically the ME gene expression, or other thyroid hormone responsive enzymes were affected as well, c) Protein/DNA complex formed on the thyroid responsive element (TRE). Livers from female Wistar rats intoxicated with HCB (100 mg/100 g b.w.), for 9 and 15 days, were analyzed. Northern blot hybridization analysis, have demonstrated that ME mRNA levels increased 4 times and 2 times after 9 and 15 days intoxication respectively, without any alterations in the mRNA levels of other thyroid hormone responsive enzymes such as glyceraldheyde 3- phosphate dehydrogenase, phosphoenolpyruvatecarboxikinase and alpha-GPD. These results suggest that HCB affects specifically, ME gene expression. Hepatic T3 and T4 levels evaluated by RIA were not affected by HCB. Scatchard analyses showed that TR affinity and number of sites were not altered after 9 and 15 days of HCB treatment (control, Ka: 1.9 nM, Bmax 3.9 f/mol 100 micrograms DNA: HCD 9 days Ka: 2.1 nM, Bmax 4.5 fmol/100 micrograms DNA: HCB 15 days Ka 1.9 nM. Bmax 5.1 fmol/100 micrograms DNA intoxication, neither at 9 nor at 15 days. Electrophoresis mobility shift assay showed that HCB did not modify nuclear protein extract affinity for the TREs sequence. Our results suggest that TR itself was not directly involved in the induction of ME gene expression by HCB. Nevertheless TR could interact with other transcription factors in the overexpression of ME gene. |
| author |
Loaiza Pérez, Andrea Irene Sancovich, Horacio Alberto Kleiman de Pisarev, Diana L. Randi, Andrea Silvana Ferramola, Ana María |
| author_facet |
Loaiza Pérez, Andrea Irene Sancovich, Horacio Alberto Kleiman de Pisarev, Diana L. Randi, Andrea Silvana Ferramola, Ana María |
| author_sort |
Loaiza Pérez, Andrea Irene |
| title |
Effect of thyroid hormones on the modulation of genetic expression of liver cytosolic malic enzyme, in rats poisoned with hexachlorobenzene |
| title_short |
Effect of thyroid hormones on the modulation of genetic expression of liver cytosolic malic enzyme, in rats poisoned with hexachlorobenzene |
| title_full |
Effect of thyroid hormones on the modulation of genetic expression of liver cytosolic malic enzyme, in rats poisoned with hexachlorobenzene |
| title_fullStr |
Effect of thyroid hormones on the modulation of genetic expression of liver cytosolic malic enzyme, in rats poisoned with hexachlorobenzene |
| title_full_unstemmed |
Effect of thyroid hormones on the modulation of genetic expression of liver cytosolic malic enzyme, in rats poisoned with hexachlorobenzene |
| title_sort |
effect of thyroid hormones on the modulation of genetic expression of liver cytosolic malic enzyme, in rats poisoned with hexachlorobenzene |
| publishDate |
1998 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03276309_v48_n3_p125_LoaizaPerez http://hdl.handle.net/20.500.12110/paper_03276309_v48_n3_p125_LoaizaPerez |
| work_keys_str_mv |
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| _version_ |
1768544821217067008 |