scholarly journals Dehydroepiandrosterone Sulfate and Allopregnanolone Directly Stimulate Catecholamine Production via Induction of Tyrosine Hydroxylase and Secretion by Affecting Actin Polymerization

Endocrinology ◽  
2005 ◽  
Vol 146 (8) ◽  
pp. 3309-3318 ◽  
Author(s):  
I. Charalampopoulos ◽  
Ε. Dermitzaki ◽  
L. Vardouli ◽  
C. Tsatsanis ◽  
C. Stournaras ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Actin Filament ◽  
Chromaffin Cells ◽  
Actin Polymerization ◽  
Dehydroepiandrosterone Sulfate ◽  
Neuroactive Steroids ◽  
Zona Reticularis ◽  
Catecholamine Synthesis ◽  
Catecholamine Levels

Abstract Adrenal cortical cells of zona reticularis produce the neuroactive steroids dehydroepiandrosterone (DHEA), its sulfate ester dehydroepiandrosterone sulfate (DHEAS), and allopregnanolone (ALLO). An interaction between zona reticularis and adrenal medulla has been postulated based on their close proximity and their interwoven borders. The aim of this paper was to examine in vitro the possible paracrine effects of these steroids on catecholamine production from adrenomedullary chromaffin cells, using an established in vitro model of chromaffin cells, the PC12 rat pheochromocytoma cell line. We have found the following: 1) DHEA, DHEAS, and ALLO increased acutely (peak effect between 10–30 min) and dose-dependently (EC50 in the nanomolar range) catecholamine levels (norepinephrine and dopamine). 2) It appears that the acute effect of these steroids involved actin depolymerization/actin filament disassembly, a fast-response cellular system regulating trafficking of catecholamine vesicles. Specifically, 10−6m phallacidin, an actin filament stabilizer, completely prevented steroid-induced catecholamine secretion. 3) DHEAS and ALLO, but not DHEA, also affected catecholamine synthesis. Indeed, DHEAS and ALLO increased catecholamine levels at 24 h, an effect blocked by l-2-methyl-3-(-4hydroxyphenyl)alanine and 3-(hydrazinomethyl)phenol hydrochloride, inhibitors of tyrosine hydroxylase and l-aromatic amino acid decarboxylase, respectively, suggesting that this effect involved catecholamine synthesis. The latter hypothesis was confirmed by finding that DHEAS and ALLO increased both the mRNA and protein levels of tyrosine hydroxylase. In conclusion, our findings suggest that neuroactive steroids exert a direct tonic effect on adrenal catecholamine synthesis and secretion. These data associate the adrenomedullary malfunction observed in old age and neuroactive steroids.

scholarly journals Urocortin 2 Lowers Blood Pressure and Reduces Plasma Catecholamine Levels in Mice with Hyperadrenergic Activity

Endocrinology ◽  
2010 ◽  
Vol 151 (10) ◽  
pp. 4820-4829 ◽  
Author(s):  
Yusu Gu ◽  
Kuixing Zhang ◽  
Nilima Biswas ◽  
Ryan S. Friese ◽  
Dennis H. Lin ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Tyrosine Hydroxylase ◽  
Plasma Levels ◽  
Catecholamine Secretion ◽  
Systemic Hypertension ◽  
Plasma Catecholamine ◽  
Wild Type ◽  
Catecholamine Synthesis ◽  
Catecholamine Levels

Exaggerated adrenergic activity is associated with human hypertension. The peptide urocortin 2 (Ucn 2) inhibits catecholamine synthesis and secretion from adrenal chromaffin cells in vitro and administration to mammals lowers blood pressure (BP). The chromogranin A-null mouse (Chga−/−) manifests systemic hypertension because of excessive catecholamine secretion from the adrenal and decreased catecholamine storage. In the present study, we investigated whether systemic administration of Ucn 2 could reduce BP and adrenal and plasma levels of catecholamines in vivo. Ucn 2 peptide was administered to freely moving, conscious Chga−/− and wild-type control mice. Telemetry and HPLC measured changes in BP and catecholamine levels, respectively. In both groups of mice, Ucn 2 dose-dependently decreased BP, and this effect was mediated by corticotropin factor-receptor type 2. However, in Chga−/− mice, the maximal percentage decrease of systolic BP from basal systolic BP was 37% compared with only a 23% reduction in wild-type mice (P = 0.04). In Chga−/− mice only, Ucn 2 decreased adrenal and plasma levels of catecholamines as well as adrenal levels of tyrosine hydroxylase protein and phosphorylation. In vitro mechanistic studies demonstrated that Ucn 2 reduces both catecholamine secretion and tyrosine hydroxylase promoter activity, suggesting that the exaggerated action of Ucn 2 to reduce BP in the Chga−/− mouse is mediated through inhibition of both catecholamine synthesis and secretion. The data suggest that Ucn 2 may be therapeutically useful in regulating the exaggerated sympathoadrenal function of hyperadrenergic hypertension.

scholarly journals Mechanisms of actin disassembly

2013 ◽  
Vol 24 (15) ◽  
pp. 2299-2302 ◽  
Author(s):  
William Brieher
Keyword(s):  
Actin Cytoskeleton ◽  
Cell Motility ◽  
Actin Filament ◽  
Actin Filaments ◽  
Actin Polymerization ◽  
Actin Depolymerization ◽  
Filament Dynamics ◽  
Physiological Demands ◽  
In Cells

The actin cytoskeleton is constantly assembling and disassembling. Cells harness the energy of these turnover dynamics to drive cell motility and organize cytoplasm. Although much is known about how cells control actin polymerization, we do not understand how actin filaments depolymerize inside cells. I briefly describe how the combination of imaging actin filament dynamics in cells and using in vitro biochemistry progressively altered our views of actin depolymerization. I describe why I do not think that the prevailing model of actin filament turnover—cofilin-mediated actin filament severing—can account for actin filament disassembly detected in cells. Finally, I speculate that cells might be able to tune the mechanism of actin depolymerization to meet physiological demands and selectively control the stabilities of different actin arrays.

scholarly journals TetraThymosinβ Is Required for Actin Dynamics in Caenorhabditis elegans and Acts via Functionally Different Actin-binding Repeats

2004 ◽  
Vol 15 (10) ◽  
pp. 4735-4748 ◽  
Author(s):  
Marleen Van Troys ◽  
Kanako Ono ◽  
Daisy Dewitte ◽  
Veronique Jonckheere ◽  
Natalie De Ruyck ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Actin Filament ◽  
Actin Polymerization ◽  
Actin Dynamics ◽  
Actin Binding ◽  
In Vitro Assays ◽  
Filamentous Actin ◽  
Lethal Mutant ◽  
Interaction Sites

Generating specific actin structures via controlled actin polymerization is a prerequisite for eukaryote development and reproduction. We here report on an essential Caenorhabditis elegans protein tetraThymosinβ expressed in developing neurons and crucial during oocyte maturation in adults. TetraThymosinβ has four repeats, each related to the actin monomer-sequestering protein thymosinβ 4 and assists in actin filament elongation. For homologues with similar multirepeat structures, a profilin-like mechanism of ushering actin onto filament barbed ends, based on the formation of a 1:1 complex, is proposed to underlie this activity. We, however, demonstrate that tetraThymosinβ binds multiple actin monomers via different repeats and in addition also interacts with filamentous actin. All repeats need to be functional for attaining full activity in various in vitro assays. The activities on actin are thus a direct consequence of the repeated structure. In containing both G- and F-actin interaction sites, tetraThymosinβ may be reminiscent of nonhomologous multimodular actin regulatory proteins implicated in actin filament dynamics. A mutation that suppresses expression of tetraThymosinβ is homozygous lethal. Mutant organisms develop into adults but display a dumpy phenotype and fail to reproduce as their oocytes lack essential actin structures. This strongly suggests that the activity of tetraThymosinβ is of crucial importance at specific developmental stages requiring actin polymerization.

scholarly journals CRMP-1 enhances EVL-mediated actin elongation to build lamellipodia and the actin cortex

2017 ◽  
Vol 216 (8) ◽  
pp. 2463-2479 ◽  
Author(s):  
Hui-Chia Yu-Kemp ◽  
James P. Kemp ◽  
William M. Brieher
Keyword(s):  
Actin Filament ◽  
Actin Polymerization ◽  
Structural Integrity ◽  
Mdck Cells ◽  
Major Contributor ◽  
Actin Assembly ◽  
Actin Cortex ◽  
Epithelial Sheets ◽  
Actin Comet Tails

Cells can control actin polymerization by nucleating new filaments or elongating existing ones. We recently identified CRMP-1 as a factor that stimulates the formation of Listeria monocytogenes actin comet tails, thereby implicating it in actin assembly. We now show that CRMP-1 is a major contributor to actin assembly in epithelial cells, where it works with the Ena/VASP family member EVL to assemble the actin cytoskeleton in the apical cortex and in protruding lamellipodia. CRMP-1 and EVL bind to one another and together accelerate actin filament barbed-end elongation. CRMP-1 also stimulates actin assembly in the presence of VASP and Mena in vitro, but CRMP-1–dependent actin assembly in MDCK cells is EVL specific. Our results identify CRMP-1 as a novel regulator of actin filament elongation and reveal a surprisingly important role for CRMP-1, EVL, and actin polymerization in maintaining the structural integrity of epithelial sheets.

scholarly journals Non Diaphanous Formin Delphilin Acts as a Barbed End Capping Protein

2016 ◽  
Author(s):  
Priyanka Dutta ◽  
Sankar Maiti
Keyword(s):  
Actin Filament ◽  
Actin Filaments ◽  
Actin Polymerization ◽  
Pdz Domains ◽  
Capping Protein ◽  
C Terminus ◽  
End Capping

ABSTRACTFormins are important for actin polymerization. Delphilin is a unique formin having PDZ domains and FH1, FH2 domains at its N and C terminus respectively. In this study we observed that Delphilin binds to actin filaments, and have negligible actin filament polymerizing activity. Delphilin inhibits actin filament elongation like barbed end capping protein CapZ. In vitro, Delphilin stabilized actin filaments by inhibiting actin filament depolymerisation. Therefore, our study demonstrates Delphilin as an actin-filament capping protein.

scholarly journals Corticotropin-Releasing Factor (CRF) and the Urocortins Differentially Regulate Catecholamine Secretion in Human and Rat Adrenals, in a CRF Receptor Type-Specific Manner

Endocrinology ◽  
2007 ◽  
Vol 148 (4) ◽  
pp. 1524-1538 ◽  
Author(s):  
E. Dermitzaki ◽  
C. Tsatsanis ◽  
V. Minas ◽  
E. Chatzaki ◽  
I. Charalampopoulos ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Chromaffin Cells ◽  
Corticotropin Releasing Factor ◽  
Receptor Type ◽  
Catecholamine Secretion ◽  
Dependent Manner ◽  
Receptor System ◽  
Catecholamine Synthesis ◽  
Receptor Agonists ◽  
Rat Adrenals

Corticotropin-releasing factor (CRF) affects catecholamine production both centrally and peripherally. The aim of the present work was to examine the presence of CRF, its related peptides, and their receptors in the medulla of human and rat adrenals and their direct effect on catecholamine synthesis and secretion. CRF, urocortin I (UCN1), urocortin II (UCN2), and CRF receptor type 1 (CRF1) and 2 (CRF2) were present in human and rat adrenal medulla as well as the PC12 pheochromocytoma cells by immunocytochemistry, immunofluorescence, and RT-PCR. Exposure of dispersed human and rat adrenal chromaffin cells to CRF1 receptor agonists induced catecholamine secretion in a dose-dependent manner, an effect peaking at 30 min, whereas CRF2 receptor agonists suppressed catecholamine secretion. The respective effects were blocked by CRF1 and CRF2 antagonists. CRF peptides affected catecholamine secretion via changes of subplasmaliminal actin filament polymerization. CRF peptides also affected catecholamine synthesis. In rat chromaffin and PC12 cells, CRF1 and CRF2 agonists induced catecholamine synthesis via tyrosine hydroxylase. However, in human chromaffin cells, activation of CRF1 receptors induced tyrosine hydroxylase, whereas activation of CRF2 suppressed it. In conclusion, it appears that a complex intraadrenal CRF-UCN/CRF-receptor system exists in both human and rat adrenals controlling catecholamine secretion and synthesis.

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