Abstract:
BACKGROUND AND PURPOSE:Mitochondria possess their own source of cAMP, that is, soluble adenylyl cyclase (sAC). Activation or expression of mitochondrial sAC promotes mitochondrial function. Oestrogen receptor signalling plays an essential role in the regulation of mitochondrial function. Here we aimed to determine whether 17β-estradiol may affect mitochondrial cAMP signalling. EXPERIMENTAL APPROACH:Expression of the intra-mitochondrial proteins (Western blot), mitochondrial cAMP content (FRET-based live imaging and MS assay), mitochondrial membrane potential and cytochrome oxidase activity were analysed in H9C2 and C2C12 cells. KEY RESULTS:A 24 h treatment with 17β-estradiol significantly reduced the basal level of mitochondrial cAMP, without affecting the intra-mitochondrial content of sAC, phosphodiesterase 2 (PDE2) or PKA and the activity of the intra-mitochondrial sAC. The effect of 17β-estradiol on mitochondrial cAMP was prevented by inhibition of a cGMP-activated PDE2 or soluble guanylyl cyclase (sGC), suggesting a role of NO signalling. Indeed, 17β-estradiol raised cellular levels of cGMP and the intra-mitochondrial expression of the catalytic subunit β of sGC was found. The 17β-estradiol-induced reduction of the mitochondrial cAMP level was accompanied by decreased cytochrome oxidase activity and mitochondrial membrane potential in a PDE2-dependent manner. CONCLUSIONS AND IMPLICATIONS:17β-estradiol reduced the basal level of mitochondrial cAMP content and cytochrome oxidase activity in a sAC-independent but in a PDE2-dependent manner. The results suggest a role of 17β-estradiol-induced activation of NO signalling in the regulation of mitochondrial cAMP content. Our study adds a new aspect to the complex action of oestrogens on mitochondrial biology, that is relevant to hormone replacement therapy.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Pozdniakova S,Guitart-Mampel M,Garrabou G,Di Benedetto G,Ladilov Y,Regitz-Zagrosek Vdoi
10.1111/bph.14455subject
Has Abstractpub_date
2018-10-01 00:00:00pages
3876-3890issue
20eissn
0007-1188issn
1476-5381journal_volume
175pub_type
杂志文章abstract::1. Nociceptin, the endogenous ORL(1) receptor agonist inhibited the motor response to electrical-field stimulation in the rat anococcygeus muscle. This effect was characterized using the peptide ligands acetyl-Arg-Tyr-Tyr-Arg-Trp-Lys-NH(2) (Ac-RYYRWK-NH(2)), acetyl-Arg-Tyr-Tyr-Arg-Ile-Lys-NH(2) (Ac-RYYRIK-NH(2)) and [...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703583
更新日期:2000-09-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13577.x
更新日期:1993-06-01 00:00:00
abstract::1. Vasorelaxant properties of three nitric oxide (NO) donor drugs (glyceryl trinitrate, sodium nitroprusside and spermine NONOate) in mouse aorta (phenylephrine pre-contracted) were compared with those of endothelium-derived NO (generated with acetylcholine), NO free radical (NO*; NO gas solution) and nitroxyl ion (NO...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704269
更新日期:2001-10-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb16254.x
更新日期:1986-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor agonists display a promising analgesic profile in preclinical studies. However, supraspinal N/OFQ produced hyperalgesia in rodents and such effects have not been addressed in primates. Thus, the aim of this study was to investigate the effects...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13124
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09274.x
更新日期:1982-09-01 00:00:00
abstract::1. The administration of an analgesic dose (10 mg/kg, s.c.) of morphine increased the concentrations of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the brains of normal mice, and the time course of the change in the DOPAC concentration corresponded approximately to t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb07236.x
更新日期:1972-01-01 00:00:00
abstract::1 The metabolism of extracellular nucleotides plays an important role in nucleotide signalling mediated by P2 receptors. The nucleotide sequence encoding a putative human ecto-ATPase named CD39L1 was reported recently. However, the biological activity of this protein has not been established. 2 Based on the sequence o...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702805
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1996.tb15680.x
更新日期:1996-09-01 00:00:00
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1975.tb07622.x
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12456.x
更新日期:1991-10-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702177
更新日期:1998-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Hypoxia/reoxygenation induces synthesis of reactive oxygen species (ROS) which can attack macromolecules and cause brain injury. The transcription factor, nuclear factor (erythroid-derived 2)-like 2, (Nrf2), ia potent activator of genes with an antioxidant responsive element and Nrf2 can countera...
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doi:10.1111/bph.13031
更新日期:2015-04-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2011-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/bph.14536
更新日期:2019-06-01 00:00:00
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doi:10.1111/j.1476-5381.2011.01486.x
更新日期:2011-11-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb09742.x
更新日期:1977-09-01 00:00:00
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doi:10.1111/j.1476-5381.2008.00009.x
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12545.x
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abstract::1. The present study was designed to evaluate the nature of intervening agents in L-DOPA- and dopamine-induced neurotoxicity in Neuro-2A cells. 2. In the absence of cells and in conditions of light protection, at 37 degrees C, L-DOPA or dopamine (1 mM) in culture medium degraded spontaneously in a time-dependent manne...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:2002-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0701541
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abstract::There is a long-known hyper-responsiveness of vascular adrenergic transmission in the spontaneously hypertensive rat (SHR) that is uncovered specifically in the presence of cocaine and attributed to blockade of the neuronal monoamine transporter. We have now used the rat anococcygeus muscle to investigate whether this...
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pub_type: 杂志文章
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更新日期:2003-10-01 00:00:00
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pub_type: 杂志文章
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更新日期:2001-01-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706774
更新日期:2006-07-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1981.tb10471.x
更新日期:1981-11-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb08792.x
更新日期:1982-02-01 00:00:00
abstract::1. The sensitivity of the guinea-pig vas deferens to noradrenaline, histamine, methylfurmethide and potassium was examined in vitro following decentralization and reserpine treatment.2. One day after decentralization or administration of reserpine (1.0 mg/kg daily) the sensitivity of the vas deferens was not increased...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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