The cAMP pathway promotes sirtuin-1 expression in human granulosa-lutein cells
| Autor: | Ketan Shrestha, Avi Harlev, Rina Meidan, Eliezer Girsh, Magdalena Szymanska, Sarah Manthe |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
0301 basic medicine animal structures endocrine system diseases Carbazoles Enzyme Activators Heterocyclic Compounds 2-Ring Cell Line Adenylyl cyclase 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology Sirtuin 1 Luteal Cells Cyclic AMP Humans RNA Small Interfering Granulosa Lutein Cell Gene knockdown Granulosa Cells 030219 obstetrics & reproductive medicine Forskolin Dose-Response Relationship Drug biology Colforsin food and beverages Phosphodiesterase Cell biology enzymes and coenzymes (carbohydrates) 030104 developmental biology chemistry Resveratrol biology.protein cAMP-dependent pathway Female Animal Science and Zoology hormones hormone substitutes and hormone antagonists Signal Transduction Developmental Biology Deacetylase activity |
| Zdroj: | Reproductive Biology. 20:273-281 |
| ISSN: | 1642-431X |
| DOI: | 10.1016/j.repbio.2020.07.010 |
| Popis: | Sirtuin-1 (SIRT1), a NAD+-dependent deacetylase, is present in the ovarian granulosa cells (GCs) of various species. This study examined the regulation of SIRT1 expression in human granulosa-lutein cells (hGLCs). Two different, structurally unrelated SIRT1 activators, SRT2104 and resveratrol, dose- and time-dependently enhanced SIRT1 (∼2- and 1.5-fold increase at 50 μmol/L for mRNA and protein levels, respectively), whereas EX-527, an inhibitor of SIRT1 deacetylase activity, significantly suppressed SIRT1 protein induced by these activators. Transfecting cells with SIRT1 siRNA molecules efficiently silenced SIRT1 (∼70 % decrease in 48 h post-transfection). Furthermore, the stimulatory effects of SRT2104 on SIRT1 expression observed in non-transfected or in scrambled siRNA-transfected cells were diminished with SIRT1 silencing. The findings described above imply that SIRT1 autoregulates its own expression. Interestingly, SRT2104 elevated cAMP accumulation (1.4-fold) in the culture media of hGLCs which was further augmented in the presence of hCG (2.2-fold); these effects were evident after 12 h of incubation. This additive effect of hCG and SRT2104 on cAMP accumulation may explain the incremental outcome observed on SIRT1 expression (∼3-fold increase from basal level and ∼1.6-fold stimulation for each compound alone) with these two compounds. SIRT1 knockdown diminished SIRT1 induced by forskolin, providing additional evidence that cAMP promotes SIRT1. These findings imply that by activating adenylyl cyclase (hCG or forskolin) and inhibiting phosphodiesterases (SIRT1 activators), these two signals converge to produce an incremental, positive feedback loop on SIRT1 expression. Such a mechanism highlights the importance of maintaining high SIRT1 levels in human luteinized GCs. |
| Databáze: | OpenAIRE |
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