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Enzyme
Compound
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Target Concepts:
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Query: EC:3.1.1.79 (
hormone-sensitive lipase
)
2,163
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The study was designed to elucidate the influence of the protein kinase A (PKA) signal transduction pathway on transcription of the LIPE gene encoding
hormone-sensitive lipase
/cholesteryl esterase (HSL) in H295R cells. HSL is one of the key enzymes involved in steroid hormone synthesis, and ACTH, with mediation of the PKA pathway, increases its activity. However, the mode of regulation of LIPE gene expression by ACTH remains unknown. It was found that stimulation of the PKA pathway by the adenylyl cyclase activator, forskolin, caused a twofold increase in LIPE transcript accompanied by appreciable rise in the protein product of the gene and cortisol output. RNA polymerase II inhibitor abolished, and protein synthesis inhibitor attenuated this effect. Forskolin and PKA catalytic subunit increased transcriptional activity of LIPE promoter A in cells transfected with the luciferase reporter vector. Overexpression of
steroidogenic factor-1
(
SF-1
) increased LIPE promoter activity, while transient silencing of
SF-1
expression with specific siRNAs abolished forskolin-stimulated LIPE transcription. It is concluded that ACTH via the PKA pathway stimulates expression of
SF-1
, which activates transcription of LIPE presumably by interaction with putative binding sequences within promoter A. A novel mechanism contributing to the long-term effect of ACTH on adrenal steroidogenesis is proposed: ACTH stimulates transcription of
SF-1
, which interacts with the putative
SF-1
-binding sequences within the promoter and activates LIPE transcription. An increased level of HSL results in an enhanced supply of cholesterol required for steroid hormone synthesis.
...
PMID:Transcription of LIPE gene encoding hormone-sensitive lipase/cholesteryl esterase is regulated by SF-1 in human adrenocortical cells: involvement of protein kinase A signal transduction pathway. 2108 92
In the adrenal cortex, corticotropin induces the expression of several genes encoding proteins involved in the synthesis and intracellular transport of steroid hormones via the protein kinase A (PKA) signalling pathway, and this process is mediated by
steroidogenic factor-1
(
SF-1
). This study was designed to elucidate the influence of the PKA and PKC pathways on the expression of the
SF-1
gene in mouse adrenocortical cells, line Y-1. It has also been attempted to answer the question whether or not
SF-1
plays a role in the PKA-induced expression of LIPE gene encoding
hormone-sensitive lipase
/cholesteryl esterase, which supplies cholesterol for steroid hormone synthesis. In this study, we found that stimulation of the PKA pathway caused a significant increase in
SF-1
expression, and that this effect was abolished by the PKA inhibitor, H89. Decreased
SF-1
gene transcript levels were seen with the simultaneous activation of PKA and PKC, suggesting a possible interaction between the PKA and PKC pathways. It was also observed that
SF-1
increased the transcriptional activity of the LIPE gene by interacting with the
SF-1
response element located in promoter A. Moreover, transient silencing of
SF-1
expression with specific siRNAs abolished PKA-stimulated transcription of the LIPE gene, indicating that
SF-1
is an important regulator of LIPE expression in Y-1 cells and thus could play a role in the regulation of the cholesterol supply for adrenal steroidogenesis.
...
PMID:SF-1 (NR5A1) expression is stimulated by the PKA pathway and is essential for the PKA-induced activation of LIPE expression in Y-1 cells. 2612 91
