Regulation of Cytosolic Sulfotransferases in Models of Human Hepatocyte Development [Articles]
Dubaisi, S., Barrett, K. G., Fang, H., Guzman-Lepe, J., Soto-Gutierrez, A., Kocarek, T. A., Runge-Morris, M.
The American Society for Pharmacology and Experimental Therapeutics (ASPET)
Published 2018
The American Society for Pharmacology and Experimental Therapeutics (ASPET)
Published 2018
| Publication Date: |
2018-07-06
|
|---|---|
| Publisher: |
The American Society for Pharmacology and Experimental Therapeutics (ASPET)
|
| Print ISSN: |
0090-9556
|
| Electronic ISSN: |
1521-009X
|
| Topics: |
Chemistry and Pharmacology
Medicine
|
| Published by: |
| _version_ | 1836398999508090880 |
|---|---|
| autor | Dubaisi, S., Barrett, K. G., Fang, H., Guzman-Lepe, J., Soto-Gutierrez, A., Kocarek, T. A., Runge-Morris, M. |
| beschreibung | Cytosolic sulfotransferases (SULTs) are expressed during early life and therefore metabolize endogenous and xenobiotic chemicals during development. Little is currently known about the regulation of individual SULTs in the developing human liver. We characterized SULT expression in primary cultures of human fetal hepatocytes and the HepaRG model of liver cell differentiation. SULT1A1 (transcript variants 1–4), SULT1C2, SULT1C4, SULT1E1, and SULT2A1 were the most abundant transcripts in human fetal hepatocytes. In HepaRG cells, SULT1B1, SULT1C2/3/4, and SULT1E1 mRNA levels increased during the transition from proliferation to confluency and then decreased as the cells underwent further differentiation. By contrast, SULT2A1 mRNA levels increased during differentiation, whereas SULT1A1 and SULT2B1 mRNA levels remained relatively constant. The temporal patterns of SULT1C2, SULT1E1, and SULT2A1 protein content were consistent with those observed at the mRNA level. To identify regulators of SULT expression, cultured fetal hepatocytes and HepaRG cells were treated with a panel of lipid- and xenobiotic-sensing receptor activators. The following effects were observed in both fetal hepatocytes and HepaRG cells: 1) liver X receptor activator treatment increased SULT1A1 transcript variant 5 levels; 2) vitamin D receptor activator treatment increased SULT1C2 and SULT2B1 mRNA levels; and 3) farnesoid X receptor activator treatment decreased SULT2A1 expression. Activators of aryl hydrocarbon receptor, constitutive androstane receptor, pregnane X receptor, and peroxisome proliferator–activated receptors produced additional gene-dependent effects on SULT expression in HepaRG cells. These findings suggest that SULT-regulating chemicals have the potential to modulate physiologic processes and susceptibility to xenobiotic stressors in the developing human liver. |
| citation_standardnr | 6299739 |
| datenlieferant | ipn_articles |
| feed_id | 1915 |
| feed_publisher | The American Society for Pharmacology and Experimental Therapeutics (ASPET) |
| feed_publisher_url | http://www.aspet.org/ |
| insertion_date | 2018-07-06 |
| journaleissn | 1521-009X |
| journalissn | 0090-9556 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | The American Society for Pharmacology and Experimental Therapeutics (ASPET) |
| quelle | Drug Metabolism and Disposition |
| relation | http://dmd.aspetjournals.org/cgi/content/short/46/8/1146?rss=1 |
| search_space | articles |
| shingle_author_1 | Dubaisi, S., Barrett, K. G., Fang, H., Guzman-Lepe, J., Soto-Gutierrez, A., Kocarek, T. A., Runge-Morris, M. |
| shingle_author_2 | Dubaisi, S., Barrett, K. G., Fang, H., Guzman-Lepe, J., Soto-Gutierrez, A., Kocarek, T. A., Runge-Morris, M. |
| shingle_author_3 | Dubaisi, S., Barrett, K. G., Fang, H., Guzman-Lepe, J., Soto-Gutierrez, A., Kocarek, T. A., Runge-Morris, M. |
| shingle_author_4 | Dubaisi, S., Barrett, K. G., Fang, H., Guzman-Lepe, J., Soto-Gutierrez, A., Kocarek, T. A., Runge-Morris, M. |
| shingle_catch_all_1 | Regulation of Cytosolic Sulfotransferases in Models of Human Hepatocyte Development [Articles] Cytosolic sulfotransferases (SULTs) are expressed during early life and therefore metabolize endogenous and xenobiotic chemicals during development. Little is currently known about the regulation of individual SULTs in the developing human liver. We characterized SULT expression in primary cultures of human fetal hepatocytes and the HepaRG model of liver cell differentiation. SULT1A1 (transcript variants 1–4), SULT1C2, SULT1C4, SULT1E1, and SULT2A1 were the most abundant transcripts in human fetal hepatocytes. In HepaRG cells, SULT1B1, SULT1C2/3/4, and SULT1E1 mRNA levels increased during the transition from proliferation to confluency and then decreased as the cells underwent further differentiation. By contrast, SULT2A1 mRNA levels increased during differentiation, whereas SULT1A1 and SULT2B1 mRNA levels remained relatively constant. The temporal patterns of SULT1C2, SULT1E1, and SULT2A1 protein content were consistent with those observed at the mRNA level. To identify regulators of SULT expression, cultured fetal hepatocytes and HepaRG cells were treated with a panel of lipid- and xenobiotic-sensing receptor activators. The following effects were observed in both fetal hepatocytes and HepaRG cells: 1) liver X receptor activator treatment increased SULT1A1 transcript variant 5 levels; 2) vitamin D receptor activator treatment increased SULT1C2 and SULT2B1 mRNA levels; and 3) farnesoid X receptor activator treatment decreased SULT2A1 expression. Activators of aryl hydrocarbon receptor, constitutive androstane receptor, pregnane X receptor, and peroxisome proliferator–activated receptors produced additional gene-dependent effects on SULT expression in HepaRG cells. These findings suggest that SULT-regulating chemicals have the potential to modulate physiologic processes and susceptibility to xenobiotic stressors in the developing human liver. Dubaisi, S., Barrett, K. G., Fang, H., Guzman-Lepe, J., Soto-Gutierrez, A., Kocarek, T. A., Runge-Morris, M. The American Society for Pharmacology and Experimental Therapeutics (ASPET) 0090-9556 00909556 1521-009X 1521009X |
| shingle_catch_all_2 | Regulation of Cytosolic Sulfotransferases in Models of Human Hepatocyte Development [Articles] Cytosolic sulfotransferases (SULTs) are expressed during early life and therefore metabolize endogenous and xenobiotic chemicals during development. Little is currently known about the regulation of individual SULTs in the developing human liver. We characterized SULT expression in primary cultures of human fetal hepatocytes and the HepaRG model of liver cell differentiation. SULT1A1 (transcript variants 1–4), SULT1C2, SULT1C4, SULT1E1, and SULT2A1 were the most abundant transcripts in human fetal hepatocytes. In HepaRG cells, SULT1B1, SULT1C2/3/4, and SULT1E1 mRNA levels increased during the transition from proliferation to confluency and then decreased as the cells underwent further differentiation. By contrast, SULT2A1 mRNA levels increased during differentiation, whereas SULT1A1 and SULT2B1 mRNA levels remained relatively constant. The temporal patterns of SULT1C2, SULT1E1, and SULT2A1 protein content were consistent with those observed at the mRNA level. To identify regulators of SULT expression, cultured fetal hepatocytes and HepaRG cells were treated with a panel of lipid- and xenobiotic-sensing receptor activators. The following effects were observed in both fetal hepatocytes and HepaRG cells: 1) liver X receptor activator treatment increased SULT1A1 transcript variant 5 levels; 2) vitamin D receptor activator treatment increased SULT1C2 and SULT2B1 mRNA levels; and 3) farnesoid X receptor activator treatment decreased SULT2A1 expression. Activators of aryl hydrocarbon receptor, constitutive androstane receptor, pregnane X receptor, and peroxisome proliferator–activated receptors produced additional gene-dependent effects on SULT expression in HepaRG cells. These findings suggest that SULT-regulating chemicals have the potential to modulate physiologic processes and susceptibility to xenobiotic stressors in the developing human liver. Dubaisi, S., Barrett, K. G., Fang, H., Guzman-Lepe, J., Soto-Gutierrez, A., Kocarek, T. A., Runge-Morris, M. The American Society for Pharmacology and Experimental Therapeutics (ASPET) 0090-9556 00909556 1521-009X 1521009X |
| shingle_catch_all_3 | Regulation of Cytosolic Sulfotransferases in Models of Human Hepatocyte Development [Articles] Cytosolic sulfotransferases (SULTs) are expressed during early life and therefore metabolize endogenous and xenobiotic chemicals during development. Little is currently known about the regulation of individual SULTs in the developing human liver. We characterized SULT expression in primary cultures of human fetal hepatocytes and the HepaRG model of liver cell differentiation. SULT1A1 (transcript variants 1–4), SULT1C2, SULT1C4, SULT1E1, and SULT2A1 were the most abundant transcripts in human fetal hepatocytes. In HepaRG cells, SULT1B1, SULT1C2/3/4, and SULT1E1 mRNA levels increased during the transition from proliferation to confluency and then decreased as the cells underwent further differentiation. By contrast, SULT2A1 mRNA levels increased during differentiation, whereas SULT1A1 and SULT2B1 mRNA levels remained relatively constant. The temporal patterns of SULT1C2, SULT1E1, and SULT2A1 protein content were consistent with those observed at the mRNA level. To identify regulators of SULT expression, cultured fetal hepatocytes and HepaRG cells were treated with a panel of lipid- and xenobiotic-sensing receptor activators. The following effects were observed in both fetal hepatocytes and HepaRG cells: 1) liver X receptor activator treatment increased SULT1A1 transcript variant 5 levels; 2) vitamin D receptor activator treatment increased SULT1C2 and SULT2B1 mRNA levels; and 3) farnesoid X receptor activator treatment decreased SULT2A1 expression. Activators of aryl hydrocarbon receptor, constitutive androstane receptor, pregnane X receptor, and peroxisome proliferator–activated receptors produced additional gene-dependent effects on SULT expression in HepaRG cells. These findings suggest that SULT-regulating chemicals have the potential to modulate physiologic processes and susceptibility to xenobiotic stressors in the developing human liver. Dubaisi, S., Barrett, K. G., Fang, H., Guzman-Lepe, J., Soto-Gutierrez, A., Kocarek, T. A., Runge-Morris, M. The American Society for Pharmacology and Experimental Therapeutics (ASPET) 0090-9556 00909556 1521-009X 1521009X |
| shingle_catch_all_4 | Regulation of Cytosolic Sulfotransferases in Models of Human Hepatocyte Development [Articles] Cytosolic sulfotransferases (SULTs) are expressed during early life and therefore metabolize endogenous and xenobiotic chemicals during development. Little is currently known about the regulation of individual SULTs in the developing human liver. We characterized SULT expression in primary cultures of human fetal hepatocytes and the HepaRG model of liver cell differentiation. SULT1A1 (transcript variants 1–4), SULT1C2, SULT1C4, SULT1E1, and SULT2A1 were the most abundant transcripts in human fetal hepatocytes. In HepaRG cells, SULT1B1, SULT1C2/3/4, and SULT1E1 mRNA levels increased during the transition from proliferation to confluency and then decreased as the cells underwent further differentiation. By contrast, SULT2A1 mRNA levels increased during differentiation, whereas SULT1A1 and SULT2B1 mRNA levels remained relatively constant. The temporal patterns of SULT1C2, SULT1E1, and SULT2A1 protein content were consistent with those observed at the mRNA level. To identify regulators of SULT expression, cultured fetal hepatocytes and HepaRG cells were treated with a panel of lipid- and xenobiotic-sensing receptor activators. The following effects were observed in both fetal hepatocytes and HepaRG cells: 1) liver X receptor activator treatment increased SULT1A1 transcript variant 5 levels; 2) vitamin D receptor activator treatment increased SULT1C2 and SULT2B1 mRNA levels; and 3) farnesoid X receptor activator treatment decreased SULT2A1 expression. Activators of aryl hydrocarbon receptor, constitutive androstane receptor, pregnane X receptor, and peroxisome proliferator–activated receptors produced additional gene-dependent effects on SULT expression in HepaRG cells. These findings suggest that SULT-regulating chemicals have the potential to modulate physiologic processes and susceptibility to xenobiotic stressors in the developing human liver. Dubaisi, S., Barrett, K. G., Fang, H., Guzman-Lepe, J., Soto-Gutierrez, A., Kocarek, T. A., Runge-Morris, M. The American Society for Pharmacology and Experimental Therapeutics (ASPET) 0090-9556 00909556 1521-009X 1521009X |
| shingle_title_1 | Regulation of Cytosolic Sulfotransferases in Models of Human Hepatocyte Development [Articles] |
| shingle_title_2 | Regulation of Cytosolic Sulfotransferases in Models of Human Hepatocyte Development [Articles] |
| shingle_title_3 | Regulation of Cytosolic Sulfotransferases in Models of Human Hepatocyte Development [Articles] |
| shingle_title_4 | Regulation of Cytosolic Sulfotransferases in Models of Human Hepatocyte Development [Articles] |
| timestamp | 2025-06-30T23:36:00.434Z |
| titel | Regulation of Cytosolic Sulfotransferases in Models of Human Hepatocyte Development [Articles] |
| titel_suche | Regulation of Cytosolic Sulfotransferases in Models of Human Hepatocyte Development [Articles] |
| topic | V WW-YZ |
| uid | ipn_articles_6299739 |