Effect of in vivo administered hexachlorobenzene on epidermal growth factor receptor levels, protein tyrosine kinase activity, and phosphotyrosine content in rat liver
In the present study, the effects of hexachlorobenzene (HCB) on epidermal growth factor receptor (EGFR) content of liver microsomes and plasma membrane, and on EGFR-tyrosine kinase activity in the microsomal fraction were investigated. In addition, we studied the parameters of the tyrosine kinase si...
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2003
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062952_v65_n9_p1495_Randi http://hdl.handle.net/20.500.12110/paper_00062952_v65_n9_p1495_Randi |
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paper:paper_00062952_v65_n9_p1495_Randi2023-06-08T14:30:34Z Effect of in vivo administered hexachlorobenzene on epidermal growth factor receptor levels, protein tyrosine kinase activity, and phosphotyrosine content in rat liver Randi, Andrea Silvana Sancovich, Horacio Alberto Ferramola, Ana María Spinelli, María Fernanda Kleiman de Pisarev, Diana L. EGFR kinase activity EGFR levels Hexachlorobenzene Phosphotyrosine content Protein tyrosine kinase Rat liver epidermal growth factor receptor hexachlorobenzene phosphotyrosine protein tyrosine kinase animal cell article cell membrane controlled study cytosol enzyme activity enzyme inhibition female liver liver cell liver microsome nonhuman priority journal protein phosphorylation rat reduction signal transduction toxicity In the present study, the effects of hexachlorobenzene (HCB) on epidermal growth factor receptor (EGFR) content of liver microsomes and plasma membrane, and on EGFR-tyrosine kinase activity in the microsomal fraction were investigated. In addition, we studied the parameters of the tyrosine kinase signalling pathway such as protein tyrosine kinase (PTK) activity and phosphotyrosine content in microsomal and cytosolic protein. To determine whether the observed alterations were correlated with a manifestation of overt toxicity, a single very low dose of HCB (1mg/kg body wt) and two much higher doses (100 and 1000mg/kg body wt), the highest being toxicologically significant in that it reduced serum thyroxine (T4) and inhibited uroporphyrinogen decarboxylase (URO-D) (EC 4.1.1.37) activity, were tested. Our results demonstrated that liver microsomes of rats treated with HCB had higher levels of EGFR than untreated rats; treated rats also had less EGFR present in hepatocyte plasma membrane fractions than did untreated rats. HCB altered the phosphotyrosine content and protein phosphorylation of some microsomal and cytosolic proteins in a biphasic dose-response relationship. At the low dose, phosphorylation and phosphotyrosine content of several microsomal proteins were increased; however, these effects were diminished or reversed at the higher doses. Our results suggest that chronic HCB treatment produces a down-regulation of the EGFR and a dose-dependent increase in EGFR-tyrosine kinase activity in the microsomal fraction. This effect may contribute to the alteration of membrane and cytosolic protein tyrosine phosphorylation. The level of sensitivity encountered in our studies is extraordinary, occurring at 1/10 to 1/1000 the doses of HCB known to cause other toxicological lesions. © 2003 Elsevier Science Inc. All rights reserved. Fil:Randi, A.S. 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:Ferramola De Sancovich, A.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Spinelli, F. 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. 2003 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062952_v65_n9_p1495_Randi http://hdl.handle.net/20.500.12110/paper_00062952_v65_n9_p1495_Randi |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
EGFR kinase activity EGFR levels Hexachlorobenzene Phosphotyrosine content Protein tyrosine kinase Rat liver epidermal growth factor receptor hexachlorobenzene phosphotyrosine protein tyrosine kinase animal cell article cell membrane controlled study cytosol enzyme activity enzyme inhibition female liver liver cell liver microsome nonhuman priority journal protein phosphorylation rat reduction signal transduction toxicity |
| spellingShingle |
EGFR kinase activity EGFR levels Hexachlorobenzene Phosphotyrosine content Protein tyrosine kinase Rat liver epidermal growth factor receptor hexachlorobenzene phosphotyrosine protein tyrosine kinase animal cell article cell membrane controlled study cytosol enzyme activity enzyme inhibition female liver liver cell liver microsome nonhuman priority journal protein phosphorylation rat reduction signal transduction toxicity Randi, Andrea Silvana Sancovich, Horacio Alberto Ferramola, Ana María Spinelli, María Fernanda Kleiman de Pisarev, Diana L. Effect of in vivo administered hexachlorobenzene on epidermal growth factor receptor levels, protein tyrosine kinase activity, and phosphotyrosine content in rat liver |
| topic_facet |
EGFR kinase activity EGFR levels Hexachlorobenzene Phosphotyrosine content Protein tyrosine kinase Rat liver epidermal growth factor receptor hexachlorobenzene phosphotyrosine protein tyrosine kinase animal cell article cell membrane controlled study cytosol enzyme activity enzyme inhibition female liver liver cell liver microsome nonhuman priority journal protein phosphorylation rat reduction signal transduction toxicity |
| description |
In the present study, the effects of hexachlorobenzene (HCB) on epidermal growth factor receptor (EGFR) content of liver microsomes and plasma membrane, and on EGFR-tyrosine kinase activity in the microsomal fraction were investigated. In addition, we studied the parameters of the tyrosine kinase signalling pathway such as protein tyrosine kinase (PTK) activity and phosphotyrosine content in microsomal and cytosolic protein. To determine whether the observed alterations were correlated with a manifestation of overt toxicity, a single very low dose of HCB (1mg/kg body wt) and two much higher doses (100 and 1000mg/kg body wt), the highest being toxicologically significant in that it reduced serum thyroxine (T4) and inhibited uroporphyrinogen decarboxylase (URO-D) (EC 4.1.1.37) activity, were tested. Our results demonstrated that liver microsomes of rats treated with HCB had higher levels of EGFR than untreated rats; treated rats also had less EGFR present in hepatocyte plasma membrane fractions than did untreated rats. HCB altered the phosphotyrosine content and protein phosphorylation of some microsomal and cytosolic proteins in a biphasic dose-response relationship. At the low dose, phosphorylation and phosphotyrosine content of several microsomal proteins were increased; however, these effects were diminished or reversed at the higher doses. Our results suggest that chronic HCB treatment produces a down-regulation of the EGFR and a dose-dependent increase in EGFR-tyrosine kinase activity in the microsomal fraction. This effect may contribute to the alteration of membrane and cytosolic protein tyrosine phosphorylation. The level of sensitivity encountered in our studies is extraordinary, occurring at 1/10 to 1/1000 the doses of HCB known to cause other toxicological lesions. © 2003 Elsevier Science Inc. All rights reserved. |
| author |
Randi, Andrea Silvana Sancovich, Horacio Alberto Ferramola, Ana María Spinelli, María Fernanda Kleiman de Pisarev, Diana L. |
| author_facet |
Randi, Andrea Silvana Sancovich, Horacio Alberto Ferramola, Ana María Spinelli, María Fernanda Kleiman de Pisarev, Diana L. |
| author_sort |
Randi, Andrea Silvana |
| title |
Effect of in vivo administered hexachlorobenzene on epidermal growth factor receptor levels, protein tyrosine kinase activity, and phosphotyrosine content in rat liver |
| title_short |
Effect of in vivo administered hexachlorobenzene on epidermal growth factor receptor levels, protein tyrosine kinase activity, and phosphotyrosine content in rat liver |
| title_full |
Effect of in vivo administered hexachlorobenzene on epidermal growth factor receptor levels, protein tyrosine kinase activity, and phosphotyrosine content in rat liver |
| title_fullStr |
Effect of in vivo administered hexachlorobenzene on epidermal growth factor receptor levels, protein tyrosine kinase activity, and phosphotyrosine content in rat liver |
| title_full_unstemmed |
Effect of in vivo administered hexachlorobenzene on epidermal growth factor receptor levels, protein tyrosine kinase activity, and phosphotyrosine content in rat liver |
| title_sort |
effect of in vivo administered hexachlorobenzene on epidermal growth factor receptor levels, protein tyrosine kinase activity, and phosphotyrosine content in rat liver |
| publishDate |
2003 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062952_v65_n9_p1495_Randi http://hdl.handle.net/20.500.12110/paper_00062952_v65_n9_p1495_Randi |
| work_keys_str_mv |
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| _version_ |
1768543876345233408 |