scholarly journals Subplasmalemmal hydrogen peroxide triggers calcium influx in gonadotropes

2018 ◽  
Vol 293 (41) ◽  
pp. 16028-16042 ◽  
Author(s):  
An K. Dang ◽  
Nathan L. Chaplin ◽  
Dilyara A. Murtazina ◽  
Ulrich Boehm ◽  
Colin M. Clay ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Calcium Channels ◽  
Nadph Oxidase ◽  
Calcium Channel ◽  
Anterior Pituitary ◽  
Calcium Influx ◽  
Ros Generation ◽  
Primary Mouse ◽  
The Impact ◽  
Stimulation Of

Gonadotropin-releasing hormone (GnRH) stimulation of its eponymous receptor on the surface of endocrine anterior pituitary gonadotrope cells (gonadotropes) initiates multiple signaling cascades that culminate in the secretion of luteinizing and follicle-stimulating hormones, which have critical roles in fertility and reproduction. Enhanced luteinizing hormone biosynthesis, a necessary event for ovulation, requires a signaling pathway characterized by calcium influx through L-type calcium channels and subsequent activation of the mitogen-activated protein kinase extracellular signal-regulated kinase (ERK). We previously reported that highly localized subplasmalemmal calcium microdomains produced by L-type calcium channels (calcium sparklets) play an essential part in GnRH-dependent ERK activation. Similar to calcium, reactive oxygen species (ROS) are ubiquitous intracellular signaling molecules whose subcellular localization determines their specificity. To investigate the potential influence of oxidant signaling in gonadotropes, here we examined the impact of ROS generation on L-type calcium channel function. Total internal reflection fluorescence (TIRF) microscopy revealed that GnRH induces spatially restricted sites of ROS generation in gonadotrope-derived αT3-1 cells. Furthermore, GnRH-dependent stimulation of L-type calcium channels required intracellular hydrogen peroxide signaling in these cells and in primary mouse gonadotropes. NADPH oxidase and mitochondrial ROS generation were each necessary for GnRH-mediated stimulation of L-type calcium channels. Congruently, GnRH increased oxidation within subplasmalemmal mitochondria, and L-type calcium channel activity correlated strongly with the presence of adjacent mitochondria. Collectively, our results provide compelling evidence that NADPH oxidase activity and mitochondria-derived hydrogen peroxide signaling play a fundamental role in GnRH-dependent stimulation of L-type calcium channels in anterior pituitary gonadotropes.

Hydrogen peroxide mediates oxidant-dependent stimulation of arterial smooth muscle L-type calcium channels

2012 ◽  
Vol 302 (9) ◽  
pp. C1382-C1393 ◽  
Author(s):  
Nathan L. Chaplin ◽  
Gregory C. Amberg
Keyword(s):  
Hydrogen Peroxide ◽  
Smooth Muscle ◽  
Calcium Channels ◽  
Calcium Influx ◽  
Redox Homeostasis ◽  
Cell Types ◽  
Ang Ii ◽  
Arterial Smooth Muscle ◽  
Biologically Relevant ◽  
Stimulation Of

Changes in calcium and redox homeostasis influence multiple cellular processes. Dysregulation of these signaling modalities is associated with pathology in cardiovascular, neuronal, endocrine, and other physiological systems. Calcium and oxidant signaling mechanisms are frequently inferred to be functionally related. To address and clarify this clinically relevant issue in the vasculature we tested the hypothesis that the ubiquitous reactive oxygen molecule hydrogen peroxide mediates oxidant-dependent stimulation of cerebral arterial smooth muscle L-type calcium channels. Using a combinatorial approach including intact arterial manipulations, electrophysiology, and total internal reflection fluorescence imaging, we found that application of physiological levels of hydrogen peroxide to isolated arterial smooth muscle cells increased localized calcium influx through L-type calcium channels. Similarly, oxidant-dependent stimulation of L-type calcium channels by the vasoconstrictor ANG II was abolished by intracellular application of catalase. Catalase also prevented ANG II from increasing localized subplasmalemmal sites of increased oxidation previously associated with colocalized calcium influx through L-type channels. Furthermore, catalase largely attenuated the contractile response of intact cerebral arterial segments to ANG II. In contrast, enhanced dismutation of superoxide to hydrogen peroxide with SOD had no effect on ANG II-dependent stimulation of L-type calcium channels. From these data we conclude that hydrogen peroxide is important for oxidant-dependent regulation of smooth muscle L-type calcium channels and arterial function. These data also support the emerging concept of hydrogen peroxide as a biologically relevant oxidant second messenger in multiple cell types with a diverse array of physiological functions.

A novel function for fibroblast growth factor 21: stimulation of NADPH oxidase-dependent ROS generation

Endocrine ◽  
2014 ◽  
Vol 49 (2) ◽  
pp. 385-395 ◽  
Author(s):  
Wen-fei Wang ◽  
Lei Ma ◽  
Ming-yao Liu ◽  
Ting-ting Zhao ◽  
Tong Zhang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Nadph Oxidase ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 21 ◽  
Ros Generation ◽  
Fibroblast Growth ◽  
Stimulation Of

scholarly journals A Systematic Review on 1, 4-Dihydropyridines and its Analogues: An Elite Scaffold

2021 ◽  
Vol 12 (3) ◽  
pp. 3117-3134
Keyword(s):  
Myocardial Infarction ◽  
Systematic Review ◽  
Clinical Trials ◽  
Calcium Channels ◽  
Calcium Channel ◽  
Calcium Channel Blockers ◽  
Calcium Influx ◽  
Channel Blockers ◽  
Neuroprotective Effects ◽  
Dihydropyridine Derivatives

1,4-Dihydropyridines are a group of pyridine-based molecules possessing a magnificent set of biological and therapeutic potentials. Belonging to the class of calcium channel blockers, they are known to be effective in the conditions, angina, hypertension, myocardial infarction and show vasodilatory and cardiac depressant effects. Hypotensive, antimicrobial, anticancer, anticoagulant, antioxidant, anticonvulsant, antimalarial, antiulcer, and neuroprotective effects have been reported with their rational use. The effects are precipitated in response to inhibition of calcium channels, gradually restricting calcium influx. Drugs like nifedipine, felodipine, and amlodipine are commonly used clinically. Several other drugs belonging to this class have been under clinical trials. The present review focuses on the various 1,4-dihydropyridine derivatives and their pharmacological actions.

Effects of osmotic swelling on voltage-gated calcium channel currents in rat anterior pituitary cells

2003 ◽  
Vol 285 (4) ◽  
pp. C840-C852 ◽  
Author(s):  
Shlomo Ben-Tabou De-Leon ◽  
Edna Blotnick ◽  
Itzhak Nussinovitch
Keyword(s):  
Calcium Channel ◽  
Calcium Influx ◽  
Membrane Surface ◽  
Hormone Secretion ◽  
Calcium Currents ◽  
Type I ◽  
Pituitary Cells ◽  
Voltage Gated ◽  
Channel Currents ◽  
Stimulation Of

Decrease in extracellular osmolarity ([Os]e) results in stimulation of hormone secretion from pituitary cells. Different mechanisms can account for this stimulation of hormone secretion. In this study we examined the possibility that hyposmolarity directly modulates voltage-gated calcium influx in pituitary cells. The effects of hyposmolarity on L-type ( IL) and T-type ( IT) calcium currents in pituitary cells were investigated by using two hyposmotic stimuli, moderate (18-22% decrease in [Os]e) and strong (31-32% decrease in [Os]e). Exposure to moderate hyposmotic stimuli resulted in three response types in IL (a decrease, a biphasic effect, and an increase in IL) and in increase in IT. Exposure to strong hyposmotic stimuli resulted only in increases in both IL and IT. Similarly, in intact pituitary cells (perforated patch method), exposure to either moderate or strong hyposmotic stimuli resulted only in increases in both IL and IT. Thus it appears that the main effect of decrease in [Os]e is increase in calcium channel currents. This increase was differential ( IL were more sensitive than IT) and voltage independent. In addition, we show that these hyposmotic effects cannot be explained by activation of an anionic conductance or by an increase in cell membrane surface area. In conclusion, this study shows that hyposmotic swelling of pituitary cells can directly modulate voltage-gated calcium influx. This hyposmotic modulation of IL and IT may contribute to the previously reported hyposmotic stimulation of hormone secretion. The mechanisms underlying these hyposmotic effects and their possible physiological relevance are discussed.

P2 receptor-mediated afferent arteriolar vasoconstriction during calcium blockade

2002 ◽  
Vol 282 (2) ◽  
pp. F245-F255 ◽  
Author(s):  
Edward W. Inscho ◽  
Anthony K. Cook
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Calcium Release ◽  
Calcium Influx ◽  
Receptor Activation ◽  
P2 Receptor ◽  
Channel Blockade ◽  
Calcium Channel Blockade ◽  
Vasoconstrictor Response ◽  
Arteriolar Diameter

Experiments were performed to determine the role of L-type calcium channels on the afferent arteriolar vasoconstrictor response to ATP and UTP. With the use of the blood-perfused juxtamedullary nephron technique, kidneys were perfused at 110 mmHg and the responses of arterioles to α,β-methylene ATP, ATP, and UTP were determined before and during calcium channel blockade with diltiazem. α,β-Methylene ATP (1.0 μM) decreased arteriolar diameter by 8 ± 1% under control conditions. This response was abolished during calcium channel blockade. In contrast, 10 μM UTP reduced afferent arteriolar diameter to a similar degree before (20 ± 4%) and during (14 ± 4%) diltiazem treatment. Additionally, diltiazem completely prevented the vasoconstriction normally observed with ATP concentrations below 10 μM and attenuated the response obtained with 10 μM ATP. These data demonstrate that L-type calcium channels play a significant role in the vasoconstrictor influences of α,β-methylene ATP and ATP but not UTP. The data also suggest that other calcium influx pathways may participate in the vasoconstrictor response evoked by P2 receptor activation. These observations support previous findings that UTP-mediated elevation of intracellular calcium concentration in preglomerular vascular smooth muscle cells relies primarily on calcium release from intracellular pools, whereas ATP-mediated responses involve both voltage-dependent calcium influx, through L-type calcium channels, and the release of calcium from intracellular stores. These results support the argument that P2X and P2Y receptors influence the diameter of afferent arterioles through activation of disparate signal transduction mechanisms.

NADPH AND NADH OXIDATION BY GUINEA PIG POLYMORPHONUCLEAR LEUCOCYTES

1963 ◽  
Vol 41 (2) ◽  
pp. 427-434 ◽  
Author(s):  
G. Y. N. Iyer ◽  
J. H. Quastel
Keyword(s):  
Hydrogen Peroxide ◽  
Guinea Pig ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Enzyme System ◽  
Polymorphonuclear Leucocytes ◽  
Hexose Monophosphate ◽  
Manganese Ions ◽  
Hexose Monophosphate Pathway ◽  
Stimulation Of

A homogenate of guinea pig polymorphonuclear leucocytes contains an enzyme system capable of oxidizing, in presence of oxygen, NADPH and NADH with the formation of hydrogen peroxide. The enzyme is much more active towards NADPH than to NADH. The presence of manganese ions strongly enhances the oxidase activity. It is suggested that the release of the NADPH oxidase in the leucocytes, during phagocytosis, accounts for the stimulation of the hexose monophosphate pathway that occurs in phagocytosis.

scholarly journals Activation of EndothelinA Receptors in Frog Adrenocortical Cells Stimulates Both Calcium Mobilization from Intracellular Stores and Calcium Influx through L-Type Calcium Channels

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 119-129 ◽  
Author(s):  
Catherine Delarue ◽  
Isabelle Remy Jouet ◽  
Marjorie Gras ◽  
Ludovic Galas ◽  
Alain Fournier ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Adenylyl Cyclase ◽  
Calcium Influx ◽  
Early Mobilization ◽  
Cytosolic Calcium ◽  
Plateau Phase ◽  
Atpase Inhibitor ◽  
Adrenocortical Cells ◽  
Corticosteroid Secretion ◽  
Stimulation Of

We have previously shown that endothelin (ET)-1 stimulates corticosterone and aldosterone secretion by the frog adrenal gland through activation of ETA receptors positively coupled to both the adenylyl cyclase and phospholipase C (PLC) pathways. The purpose of the present study was to investigate the involvement of calcium in ET-1-induced stimulation of corticosteroid secretion. Cytoautoradiographic labeling using [125I]ET-1 as a tracer revealed the presence of ET-1 binding sites on adrenocortical cells. Administration of graded concentrations of ET-1 in the vicinity of adrenocortical cells provoked a dose-dependent increase in cytosolic calcium concentrations ([Ca2+]i). ET-1 induced a biphasic response consisting of an immediate and transient peak of [Ca2+]i followed by a plateau phase. Preincubation of the cells with the calcium-ATPase inhibitor thapsigargin or the PLC inhibitor U-73122 reduced the amplitude of the transient phase. Administration of the calcium chelator EGTA or the protein kinase A inhibitor H-89 attenuated the plateau phase. The [Ca2+]i response to ET-1 was markedly reduced during concomitant administration of U-73122 and H-89. Preincubation of the cells with the L-type calcium channel blocker nifedipine attenuated the plateau phase. Corticosteroid secretion from perifused frog adrenal slices was almost completely suppressed by thapsigargin and reduced by nifedipine. Taken together, these data indicate that activation of ETA receptors in frog adrenocortical cells provokes immediate stimulation of PLC, which causes an early mobilization of calcium from intracellular stores, and activates adenylyl cyclase, which results in delayed calcium influx through L-type calcium channels. The resulting increase in [Ca2+]i plays a pivotal role in ET-1-induced corticosteroid secretion.

Phagocyte NADPH oxidase and specific immunity

2015 ◽  
Vol 128 (10) ◽  
pp. 635-648 ◽  
Author(s):  
Julien Cachat ◽  
Christine Deffert ◽  
Stephanie Hugues ◽  
Karl-Heinz Krause
Keyword(s):  
Dendritic Cells ◽  
Nadph Oxidase ◽  
Cell Fate ◽  
B Lymphocytes ◽  
Antigen Processing ◽  
Ros Generation ◽  
Cell Fate Decisions ◽  
Specific Immunity ◽  
Phagocyte Nadph Oxidase ◽  
The Impact

The phagocyte NADPH oxidase NOX2 produces reactive oxygen species (ROS) and is a well-known player in host defence. However, there is also increasing evidence for a regulatory role of NOX2 in adaptive immunity. Deficiency in phagocyte NADPH oxidase causes chronic granulomatous disease (CGD) in humans, a condition that can also be studied in CGD mice. Clinical observations in CGD patients suggest a higher susceptibility to autoimmune diseases, in particular lupus, idiopathic thrombocytopenic purpura and rheumatoid arthritis. In mice, a strong correlation exists between a polymorphism in a NOX2 subunit and the development of autoimmune arthritis. NOX2 deficiency in mice also favours lupus development. Both CGD patients and CGD mice exhibit increased levels of immunoglobulins, including autoantibodies. Despite these phenotypes suggesting a role for NOX2 in specific immunity, mechanistic explanations for the typical increase of CGD in autoimmune disease and antibody levels are still preliminary. NOX2-dependent ROS generation is well documented for dendritic cells and B-lymphocytes. It is unclear whether T-lymphocytes produce ROS themselves or whether they are exposed to ROS derived from dendritic cells during the process of antigen presentation. ROS are signalling molecules in virtually any cell type, including T- and B-lymphocytes. However, knowledge about the impact of ROS-dependent signalling on T- and B-lymphocyte phenotype and response is still limited. ROS might contribute to Th1/Th2/Th17 cell fate decisions during T-lymphocyte activation and might enhance immunoglobulin production by B-lymphocytes. In dendritic cells, NOX2-derived ROS might be important for antigen processing and cell activation.

scholarly journals Interactions between proteins implicated in exocytosis and voltage–gated calcium channels

1999 ◽  
Vol 354 (1381) ◽  
pp. 289-297 ◽  
Author(s):  
Michael Seagar ◽  
Christian Lévêque ◽  
Nathalie Charvin ◽  
Beatrice Marquèze ◽  
Nicole Martin–Moutot ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Molecular Chaperones ◽  
Synaptic Vesicles ◽  
Calcium Influx ◽  
Voltage Gated ◽  
Interaction Sites ◽  
Synaptotagmin I ◽  
Direct Assembly ◽  
A Subunit

Neurotransmitter release from synaptic vesicles is triggered by voltage–gated calcium influx through P/Q–type or N–type calcium channels. Purification of N–type channels from rat brain synaptosomes initially suggested molecular interactions between calcium channels and two key proteins implicated in exocytosis: synaptotagmin I and syntaxin 1. Co–immunoprecipitation experiments were consistent with the hypothesis that both N– and P/Q–type calcium channels, but not L–type channels, are associated with the 7S complex containing syntaxin 1, SNAP–25, VAMP and synaptotagmin I or II. Immunofluorescence confocal microscopy at the frog neuromuscular junction confirmed that calcium channels, syntaxin 1 and SNAP–25 are co–localized at active zones of the presynaptic plasma membrane where transmitter release occurs. Experiments with recombinant proteins were performed to map synaptic protein interaction sites on the α 1 A subunit, which forms the pore of the P/Q–type calcium channel. In vitro –translated 35 S–synaptotagmin I bound to a site located on the cytoplasmic loop linking homologous domains II and III of the α 1 A subunit. This direct link would target synaptotagmin, a putative calcium sensor for exocytosis, to a microdomain of calcium influx close to the channel mouth. Cysteine string proteins (CSPs) contain a J–domain characteristic of molecular chaperones that co–operate with Hsp70. They are located on synaptic vesicles and thought to be involved in modulating the acticity of presynaptic calcium channels. CSPs were found to bind to the same domain of the calcium channel as synaptotagmin, and also to associate with VAMP. CSPs may act as molecular chaperones in association with Hsp70 to direct assembly or dissociation of multi–protein complexes at the calcium channel.

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