CIDeRplusGeneral Information:
| Id: | 4,596 |
| Diseases: |
Diabetes mellitus, type II
- [OMIM]
Insulin resistance |
| Homo sapiens | |
| article | |
| Reference: | Grasfeder LL et al.(2009) Fasting-induced hepatic production of DHEA is regulated by PGC-1alpha, ERRalpha, and HNF4alpha Mol. Endocrinol. 8: 1171-1182 [PMID: 19389810] |
Interaction Information:
| Comment | CYP11A1 and CYP17A1, rate-limiting enzymes in steroidogenesis, are functionally induced in human hepatic cells by PGC-1alpha. |
|
Formal Description Interaction-ID: 45720 |
|
| Drugbank entries | Show/Hide entries for CYP11A1 |
| Comment | CYP11A1 and CYP17A1, rate-limiting enzymes in steroidogenesis, are functionally induced in human hepatic cells by PGC-1alpha. |
|
Formal Description Interaction-ID: 45721 |
|
| Drugbank entries | Show/Hide entries for CYP17A1 |
| Comment | Both CYP11A1 and CYP17A1 require additional proteins and redox partners for their enzymatic activity. CYP11A1 requires ferridoxin reductase (FDXR) and ferridoxin, whereas the p450 oxidoreductase (POR) and cytochrome b5 are obligate partners of CYP17A1. PGC-1alpha increases the functional activity of CYP11A1 and CYP17A1. |
|
Formal Description Interaction-ID: 45722 |
|
| Drugbank entries | Show/Hide entries for CYP11A1 |
| Comment | Both CYP11A1 and CYP17A1 require additional proteins and redox partners for their enzymatic activity. CYP11A1 requires ferridoxin reductase (FDXR) and ferridoxin, whereas the p450 oxidoreductase (POR) and cytochrome b5 are obligate partners of CYP17A1. PGC-1alpha increases the functional activity of CYP11A1 and CYP17A1. |
|
Formal Description Interaction-ID: 45723 |
|
| Drugbank entries | Show/Hide entries for CYP17A1 |
| Comment | PGC-1alpha-dependent induction of CYP11A1 and CYP17A1 requires ERR-alpha. |
|
Formal Description Interaction-ID: 45724 |
|
| Drugbank entries | Show/Hide entries for ESRRA or CYP11A1 |
| Comment | PGC-1alpha-dependent induction of CYP11A1 and CYP17A1 requires ERR-alpha. |
|
Formal Description Interaction-ID: 45725 |
|
| Drugbank entries | Show/Hide entries for ESRRA or CYP17A1 |
| Comment | HNF4-alpha is required for maximal induction of CYP17A1 by PGC-1alpha. |
|
Formal Description Interaction-ID: 45726 |
|
| Drugbank entries | Show/Hide entries for HNF4A or CYP17A1 |
| Comment | Dehydroepiandrosterone (DHEA) is a product of CYP17A1 activity and is a predominant steroid resulting from overexpression of PGC-1alpha in HepG2 cells. |
|
Formal Description Interaction-ID: 45727 |
|
| Drugbank entries | Show/Hide entries for CYP17A1 or Dehydroepiandrosterone |
| Comment | The study tested whether low concentrations of dehydroepiandrosterone (DHEA) might have an impact on any relevant metabolic markers in hepatic cells. HepG2 cells were treated with 1 nM DHEA, and tandem mass spectrometry was used to measure various metabolic parameters of the cells, including acylcarnitines and amino acids. No changes in acylcarnitines were evident. However, although glycine, serine, proline, and aspartate levels did not change in treated cells, we reproducibly observed that the levels of alanine, arginine, valine, leucine, isoleucine, tyrosine, phenylalanine, methionine, and histidine levels were reduced about 50% by 1 nM DHEA. |
|
Formal Description Interaction-ID: 45730 |
drug/chemical compound NOT affects_quantity of drug/chemical compound Fatty acid acylcarnitine |
| Drugbank entries | Show/Hide entries for Dehydroepiandrosterone |
| Comment | The study tested whether low concentrations of dehydroepiandrosterone (DHEA) might have an impact on any relevant metabolic markers in hepatic cells. HepG2 cells were treated with 1 nM DHEA, and tandem mass spectrometry was used to measure various metabolic parameters of the cells, including acylcarnitines and amino acids. No changes in acylcarnitines were evident. However, although glycine, serine, proline, and aspartate levels did not change in treated cells, we reproducibly observed that the levels of alanine, arginine, valine, leucine, isoleucine, tyrosine, phenylalanine, methionine, and histidine levels were reduced about 50% by 1 nM DHEA. |
|
Formal Description Interaction-ID: 45731 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Dehydroepiandrosterone |
| Comment | The study tested whether low concentrations of dehydroepiandrosterone (DHEA) might have an impact on any relevant metabolic markers in hepatic cells. HepG2 cells were treated with 1 nM DHEA, and tandem mass spectrometry was used to measure various metabolic parameters of the cells, including acylcarnitines and amino acids. No changes in acylcarnitines were evident. However, although glycine, serine, proline, and aspartate levels did not change in treated cells, we reproducibly observed that the levels of alanine, arginine, valine, leucine, isoleucine, tyrosine, phenylalanine, methionine, and histidine levels were reduced about 50% by 1 nM DHEA. |
|
Formal Description Interaction-ID: 45732 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Dehydroepiandrosterone |
| Comment | The study tested whether low concentrations of dehydroepiandrosterone (DHEA) might have an impact on any relevant metabolic markers in hepatic cells. HepG2 cells were treated with 1 nM DHEA, and tandem mass spectrometry was used to measure various metabolic parameters of the cells, including acylcarnitines and amino acids. No changes in acylcarnitines were evident. However, although glycine, serine, proline, and aspartate levels did not change in treated cells, we reproducibly observed that the levels of alanine, arginine, valine, leucine, isoleucine, tyrosine, phenylalanine, methionine, and histidine levels were reduced about 50% by 1 nM DHEA. |
|
Formal Description Interaction-ID: 45733 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Dehydroepiandrosterone |
| Comment | The study tested whether low concentrations of dehydroepiandrosterone (DHEA) might have an impact on any relevant metabolic markers in hepatic cells. HepG2 cells were treated with 1 nM DHEA, and tandem mass spectrometry was used to measure various metabolic parameters of the cells, including acylcarnitines and amino acids. No changes in acylcarnitines were evident. However, although glycine, serine, proline, and aspartate levels did not change in treated cells, we reproducibly observed that the levels of alanine, arginine, valine, leucine, isoleucine, tyrosine, phenylalanine, methionine, and histidine levels were reduced about 50% by 1 nM DHEA. |
|
Formal Description Interaction-ID: 45734 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Dehydroepiandrosterone |
| Comment | The study tested whether low concentrations of dehydroepiandrosterone (DHEA) might have an impact on any relevant metabolic markers in hepatic cells. HepG2 cells were treated with 1 nM DHEA, and tandem mass spectrometry was used to measure various metabolic parameters of the cells, including acylcarnitines and amino acids. No changes in acylcarnitines were evident. However, although glycine, serine, proline, and aspartate levels did not change in treated cells, we reproducibly observed that the levels of alanine, arginine, valine, leucine, isoleucine, tyrosine, phenylalanine, methionine, and histidine levels were reduced about 50% by 1 nM DHEA. |
|
Formal Description Interaction-ID: 45735 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Dehydroepiandrosterone |
| Comment | The study tested whether low concentrations of dehydroepiandrosterone (DHEA) might have an impact on any relevant metabolic markers in hepatic cells. HepG2 cells were treated with 1 nM DHEA, and tandem mass spectrometry was used to measure various metabolic parameters of the cells, including acylcarnitines and amino acids. No changes in acylcarnitines were evident. However, although glycine, serine, proline, and aspartate levels did not change in treated cells, we reproducibly observed that the levels of alanine, arginine, valine, leucine, isoleucine, tyrosine, phenylalanine, methionine, and histidine levels were reduced about 50% by 1 nM DHEA. |
|
Formal Description Interaction-ID: 45736 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Dehydroepiandrosterone |
| Comment | The study tested whether low concentrations of dehydroepiandrosterone (DHEA) might have an impact on any relevant metabolic markers in hepatic cells. HepG2 cells were treated with 1 nM DHEA, and tandem mass spectrometry was used to measure various metabolic parameters of the cells, including acylcarnitines and amino acids. No changes in acylcarnitines were evident. However, although glycine, serine, proline, and aspartate levels did not change in treated cells, we reproducibly observed that the levels of alanine, arginine, valine, leucine, isoleucine, tyrosine, phenylalanine, methionine, and histidine levels were reduced about 50% by 1 nM DHEA. |
|
Formal Description Interaction-ID: 45737 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Dehydroepiandrosterone |
| Comment | The study tested whether low concentrations of dehydroepiandrosterone (DHEA) might have an impact on any relevant metabolic markers in hepatic cells. HepG2 cells were treated with 1 nM DHEA, and tandem mass spectrometry was used to measure various metabolic parameters of the cells, including acylcarnitines and amino acids. No changes in acylcarnitines were evident. However, although glycine, serine, proline, and aspartate levels did not change in treated cells, we reproducibly observed that the levels of alanine, arginine, valine, leucine, isoleucine, tyrosine, phenylalanine, methionine, and histidine levels were reduced about 50% by 1 nM DHEA. |
|
Formal Description Interaction-ID: 45738 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Dehydroepiandrosterone |
| Comment | The study tested whether low concentrations of dehydroepiandrosterone (DHEA) might have an impact on any relevant metabolic markers in hepatic cells. HepG2 cells were treated with 1 nM DHEA, and tandem mass spectrometry was used to measure various metabolic parameters of the cells, including acylcarnitines and amino acids. No changes in acylcarnitines were evident. However, although glycine, serine, proline, and aspartate levels did not change in treated cells, we reproducibly observed that the levels of alanine, arginine, valine, leucine, isoleucine, tyrosine, phenylalanine, methionine, and histidine levels were reduced about 50% by 1 nM DHEA. |
|
Formal Description Interaction-ID: 45739 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Dehydroepiandrosterone |
| Comment | The study tested whether low concentrations of dehydroepiandrosterone (DHEA) might have an impact on any relevant metabolic markers in hepatic cells. HepG2 cells were treated with 1 nM DHEA, and tandem mass spectrometry was used to measure various metabolic parameters of the cells, including acylcarnitines and amino acids. No changes in acylcarnitines were evident. However, although glycine, serine, proline, and aspartate levels did not change in treated cells, we reproducibly observed that the levels of alanine, arginine, valine, leucine, isoleucine, tyrosine, phenylalanine, methionine, and histidine levels were reduced about 50% by 1 nM DHEA. |
|
Formal Description Interaction-ID: 45740 |
drug/chemical compound NOT affects_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Dehydroepiandrosterone or Glycine |
| Comment | The study tested whether low concentrations of dehydroepiandrosterone (DHEA) might have an impact on any relevant metabolic markers in hepatic cells. HepG2 cells were treated with 1 nM DHEA, and tandem mass spectrometry was used to measure various metabolic parameters of the cells, including acylcarnitines and amino acids. No changes in acylcarnitines were evident. However, although glycine, serine, proline, and aspartate levels did not change in treated cells, we reproducibly observed that the levels of alanine, arginine, valine, leucine, isoleucine, tyrosine, phenylalanine, methionine, and histidine levels were reduced about 50% by 1 nM DHEA. |
|
Formal Description Interaction-ID: 45741 |
drug/chemical compound NOT affects_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Dehydroepiandrosterone |
| Comment | The study tested whether low concentrations of dehydroepiandrosterone (DHEA) might have an impact on any relevant metabolic markers in hepatic cells. HepG2 cells were treated with 1 nM DHEA, and tandem mass spectrometry was used to measure various metabolic parameters of the cells, including acylcarnitines and amino acids. No changes in acylcarnitines were evident. However, although glycine, serine, proline, and aspartate levels did not change in treated cells, we reproducibly observed that the levels of alanine, arginine, valine, leucine, isoleucine, tyrosine, phenylalanine, methionine, and histidine levels were reduced about 50% by 1 nM DHEA. |
|
Formal Description Interaction-ID: 45742 |
drug/chemical compound NOT affects_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Dehydroepiandrosterone |
| Comment | The study tested whether low concentrations of dehydroepiandrosterone (DHEA) might have an impact on any relevant metabolic markers in hepatic cells. HepG2 cells were treated with 1 nM DHEA, and tandem mass spectrometry was used to measure various metabolic parameters of the cells, including acylcarnitines and amino acids. No changes in acylcarnitines were evident. However, although glycine, serine, proline, and aspartate levels did not change in treated cells, we reproducibly observed that the levels of alanine, arginine, valine, leucine, isoleucine, tyrosine, phenylalanine, methionine, and histidine levels were reduced about 50% by 1 nM DHEA. |
|
Formal Description Interaction-ID: 45743 |
drug/chemical compound NOT affects_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Dehydroepiandrosterone |
| Comment | The results indicate that DHEA is synthesized in HepG2 cells when PGC-1alpha is expressed. However, downstream conversion of this steroid to androgens, such as androstenedione or testosterone, was not observed. This was in agreement with the fact that no significant expression of 3-hydroxysteroid dehydrogenase1 or 2 in un-manipulated cells or those expressing PGC-1alpha was detected. It is therefore tempting to speculate that the primary purpose of these enzymes during fasting is to produce DHEA and that it has an important role in the regulation of liver metabolism. |
|
Formal Description Interaction-ID: 45744 |
|
| Drugbank entries | Show/Hide entries for HSD3B1 |
| Comment | The results indicate that DHEA is synthesized in HepG2 cells when PGC-1alpha is expressed. However, downstream conversion of this steroid to androgens, such as androstenedione or testosterone, was not observed. This was in agreement with the fact that no significant expression of 3-hydroxysteroid dehydrogenase1 or 2 in un-manipulated cells or those expressing PGC-1alpha was detected. It is therefore tempting to speculate that the primary purpose of these enzymes during fasting is to produce DHEA and that it has an important role in the regulation of liver metabolism. |
|
Formal Description Interaction-ID: 45745 |
|
| Drugbank entries | Show/Hide entries for HSD3B2 |