12-lipoxygenase pathway increases aldosterone production, 3',5'-cyclic adenosine monophosphate response element-binding protein phosphorylation, and p38 mitogen-activated protein kinase activation in H295R human adrenocortical cells
| Autor: | Yeshao Wen, Jerry L. Nadler, Angeles Mison, Jiali Gu |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Aldosterone synthase
medicine.medical_specialty medicine.drug_class Activating transcription factor Nerve Tissue Proteins CREB Arachidonate 12-Lipoxygenase p38 Mitogen-Activated Protein Kinases Gene Expression Regulation Enzymologic chemistry.chemical_compound Endocrinology Genes Reporter Internal medicine medicine Cytochrome P-450 CYP11B2 Humans Vasoconstrictor Agents Cyclic adenosine monophosphate 12-Hydroxy-5 8 10 14-eicosatetraenoic Acid Phosphorylation Cyclic AMP Response Element-Binding Protein Luciferases Aldosterone Cells Cultured Adaptor Proteins Signal Transducing Activating Transcription Factor 1 Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 biology Angiotensin II DNA-Binding Proteins chemistry Mineralocorticoid biology.protein Adrenal Cortex Mitogen-Activated Protein Kinases Carrier Proteins Transcription Factors |
| Zdroj: | Endocrinology. 144(2) |
| ISSN: | 0013-7227 |
| Popis: | Evidence suggests that the 12-lipoxygenase (LO) pathway mediates angiotensin II (Ang II)-induced aldosterone synthesis in adrenal glomerulosa cells. To study the mechanisms of 12-LO pathway on aldosterone synthesis, the human adrenocortical cell line, H295R, was transiently transfected with a mouse leukocyte type of 12-LO. Overexpression of 12-LO stimulated aldosterone production 2.7-fold as well as the reporter gene activity of CYP11B2 gene-encoding human aldosterone synthase by 5-fold over that in mock-transfected cells. Ang II further enhanced aldosterone production, which could be blocked by a 12-LO inhibitor, baicalein, in mock cells and cells overexpressing 12-LO. Ang II stimulated cAMP response element-binding protein (CREB) phosphorylation in a dose- and time-dependent fashion in parent H295R cells. Overexpression of 12-LO increased phosphorylation of CREB/activating transcription factor (ATF)-1 1.5-fold over that in mock cells under basal conditions. Ang II led to a further 5.2- and 7.5-fold increase in mock cells and 12-LO cells, respectively. Overexpression of 12-LO induced p38 MAPK activation. The 12-LO product, 12-hydroxyeicosatetraenoic acid, increased phosphorylation of CREB/ATF-1 3.6-fold and phosphorylation of p38 MAPK 8-fold over basal. The p38 MAPK inhibitor SB203580 inhibited Ang II- and 12-LO pathway-induced phosphorylated CREB/ATF-1, suggesting a role of p38 MAPK in Ang II and 12-LO pathway signaling. These results suggest that 12-LO stimulation leads to aldosterone production in H295R cells in part through activation of CREB/ATF-1 and p38 MAPK pathway. |
| Databáze: | OpenAIRE |
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