Lysosomal-type PLA2and turnover of alveolar DPPC

2001 ◽  
Vol 280 (4) ◽  
pp. L748-L754 ◽  
Author(s):  
Aron B. Fisher ◽  
Chandra Dodia
Keyword(s):  
Degradation Products ◽  
Specific Inhibitor ◽  
Rat Lung ◽  
Lamellar Bodies ◽  
Lung Uptake ◽  
Rat Lungs ◽  
Choline Incorporation ◽  
Total Tissue ◽  
Intact Rats

This study evaluated the role of a lysosomal-type phospholipase A2(aiPLA2) in the degradation of internalized dipalmitoylphosphatidylcholine (DPPC) and in phospholipid synthesis by the rat lung. Uptake and degradation of DPPC were measured in isolated perfused rat lungs over 3 h following endotracheal instillation of [3H]DPPC in mixed unilamellar liposomes plus or minus MJ33, a specific inhibitor of lung aiPLA2. Uptake of DPPC was calculated from total tissue-associated radiolabel, and degradation was calculated from the sum of radiolabel in degradation products. Both uptake and degradation were markedly stimulated by addition of 8-bromo-cAMP to the perfusate. MJ33 had no effect on DPPC uptake but decreased DPPC degradation at 3 h by ∼40–50%. The effect of MJ33 on lung synthesis of DPPC was evaluated with intact rats over a 12- to 24-h period following intravenous injection of radiolabeled palmitate and choline. MJ33 treatment decreased palmitate incorporation into disaturated phosphatidylcholine of lamellar bodies and surfactant by ∼65% at 24 h but had no effect on choline incorporation. This result is compatible with inhibition of the deacylation/reacylation pathway for DPPC synthesis. These results obtained with intact rat lungs indicate that aiPLA2is a major enzyme for degradation of internalized DPPC and also has an important role in DPPC synthesis.

Precursor utilization of 5-hydroxytryptophan for 5-hydroxytryptamine biosynthesis in isolated and perfused rabbit and rat lungs

1987 ◽  
Vol 65 (10) ◽  
pp. 2117-2123 ◽  
Author(s):  
Kodavanti S. Prasada Rao ◽  
Harihara M. Mehendale
Keyword(s):  
Acetic Acid ◽  
Lung Perfusion ◽  
Significant Inhibition ◽  
The Other ◽  
Rat Lung ◽  
Lung Uptake ◽  
Rabbit Lung ◽  
Rat Lungs ◽  
Circulating Levels

The present study was designed to investigate whether lungs can utilize 5-hydroxytryptophan (5-HTP), formed elsewhere and transported, for the synthesis of 5-hydroxytryptamine (5-HT). [14C]5-HTP uptake was 7.7 ± 1.1 and 3.9 ± 0.2% by rabbit and rat lungs, respectively, after 1 h of perfusion with 10 μM [14C]5-HTP. There was an increase in the lung uptake of [14C]5-HTP when the lungs were preperfused with 0.5 mM chlorphentermine (CP) and the uptake was low when the lungs were preperfused with 0.1 mM hydroxybenzylhydrazine dihydrochloride (HBH). The perfusate concentration of 5-hydroxyindole acetic acid (5-HIAA) increased significantly (3–4 μg/100 mL) during rabbit lung perfusion with 10 μM [14C]5-HTP and this did not change significantly when the lungs were preperfused with 0.5 mM CP. However, 5-HT increased with time in the perfusate, 5-HT, but not 5-HIAA, was detected in the perfusate and increased with time of perfusion when the rat lungs were perfused either with 10 μM 5-HTP or with 0.5 mM CP and 10 μM 5-HTP. However, no metabolites were detected in either the rabbit lung or rat lung perfusates when they were preperfused with 0.1 mM HBH. Lung contents of 5-HT and 5-HIAA were significantly higher in the rat lungs and only 5-HIAA increased in rabbit lungs after 1 h of perfusion with 10 μM 5-HTP. Preperfusion with 0.5 mM CP resulted in a greater increase in the 5-HT content of both rabbit and rat lungs. When the lungs were preperfused with 0.1 mM HBH, [14C]5-HT formation from [14C]5-HTP was obtunded. Homogenates of rabbit and rat lungs incubated with [14C]5-HTP (10 μM) resulted in the formation of substantial amounts of [14C]5-HT and [14C]5-HIAA. Incubations with CP (0.5 or 1 mM) resulted in significant increases of 5-HT levels and a corresponding significant reduction in 5-HIAA levels. On the other hand, incubations with HBH (0.1 mM) resulted in significant inhibition of 5-HT and 5-HIAA formation. 5-HT formation from 5-HTP by rat and rabbit lungs in in vitro incubations is in consonance with the perfusion experiments. These results provide evidence that lung can synthesize 5-HT from the circulating 5-HTP, and pulmonary contribution of 5-HT to the circulating levels is possible.

Effects of steroid hormones on cyclic adenosine 3′,5′-monophosphate levels in the rat lung

1992 ◽  
Vol 134 (1) ◽  
pp. 73-76 ◽  
Author(s):  
B. M. Nabishah ◽  
B. A. K. Khalid ◽  
P. B. Morat ◽  
A. K. Alias ◽  
M. Zainuddin
Keyword(s):  
Steroid Hormones ◽  
Progesterone Receptors ◽  
Female Rats ◽  
Male Rats ◽  
Normal Female ◽  
Rat Lung ◽  
Camp Content ◽  
Rat Lungs ◽  
Camp Levels

ABSTRACT The possible role of cyclic adenosine 3′,5′-monophosphate (cAMP) in mediating the action of steroid hormones was investigated using the rat lung. Male rats were adrenalectomized and treated with olive oil, dexamethasone, corticosterone, deoxycorticosterone (DOC) or progesterone. At the end of 10 days, 100 μg isoprenaline/kg was injected intraperitoneally 5 min before the animals were killed to stimulate cAMP production. Adrenalectomy significantly decreased cAMP levels in the rat lung. Dexamethasone and corticosterone pretreatment reversed the effect of adrenalectomy whereas progesterone pretreatment but not DOC pretreatment significantly decreased lung cAMP levels. Cyclic AMP levels in normal female rats, whether pregnant or not, were not significantly different from those in male rats. We concluded that the absence of glucocorticoid, as after adrenalectomy, decreased the cAMP levels in rat lungs and that this could be reversed by either dexamethasone or corticosterone replacement. Progesterone reduced the cAMP content in rat lungs by acting as a glucocorticoid antagonist or by acting directly via progesterone receptors. Journal of Endocrinology (1992) 134, 73–76

scholarly journals Surfactant protein A is localized at the corners of the pulmonary tubular myelin lattice.

1991 ◽  
Vol 39 (10) ◽  
pp. 1331-1336 ◽  
Author(s):  
W F Voorhout ◽  
T Veenendaal ◽  
H P Haagsman ◽  
A J Verkleij ◽  
L M van Golde ◽  
...  
Keyword(s):  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Alveolar Type ◽  
Type Ii ◽  
Rat Lung ◽  
Lamellar Bodies ◽  
20 Nm

Immunogold labeling on sections of a freeze-substituted tubular myelin-enriched fraction isolated from a bronchoalveolar lavage of rat lung showed that surfactant protein A (SP-A) occurs predominantly at the corners of the tubular myelin lattice. Seventy-nine percent of the gold particles were located within 20 nm from a corner. Extracellular SP-A was detected only in the tubular myelin lattice and not in vesicles or secreted lamellar bodies. Ultra-thin cryosections of rat lung fixed in vivo showed that intracellular SP-A was distributed homogeneously over the stacked membranes of lamellar bodies in alveolar Type II cells. The presence of SP-A at the corners of the tubular myelin lattice suggests an important role of this protein in the formation and/or maintenance of this highly ordered lattice.

scholarly journals Effect of orally administered glutathione on glutathione levels in some organs of rats: role of specific transporters

1997 ◽  
Vol 78 (2) ◽  
pp. 293-300 ◽  
Author(s):  
Fabio Favilli ◽  
Patrizia Marraccini ◽  
Teresa Iantomasi ◽  
Maria T. Vincenzini
Keyword(s):  
Amino Acids ◽  
Oral Administration ◽  
Degradation Products ◽  
Specific Inhibitor ◽  
Buthionine Sulfoximine ◽  
Transport Systems ◽  
Rat Jejunum ◽  
Equivalent Amount ◽  
Specific Transport

The present study reports data on absorption of orally administered glutathione (GSH) in rat jejunum and in other organs, and the possible role of specific transport systems of GSH and γ-glutamyltranspeptidase (EC 2.3.2.1; γ-GT) activity. GSH levels were measured simultaneously in various organs after oral GSH administration to untreated rats and rats treated with L-buthionine sulfoximine (BSO) or acivicin (AT125). BSO selectively inhibits GSH intracellular synthesis and AT125 is a specific inhibitor of γ-GT activity. GSH levels were also measured after oral administration of an equivalent amount of the constituent amino acids of GSH to untreated and BSO-treated rats. Significant increases in GSH levels were found in jejunum, lung, heart, liver and brain after oral GSH administration to untreated rats. GSH increases were also obtained in all organs, except liver, when GSH was administered to rats previously GHS-depleted by treatment with BSO. The analysis of all results allowed us to distinguish between the increase in GSH intracellular levels due to intact GSH uptake by specific transporters, and that due to GSH degradation by γ-GT activity and subsequent absorption of degradation products with intracellular resynthesis of GSH; both these mechanisms seemed to be involved in increasing GSH content in heart after oral GSH administration. Jejunum, lung and brain took up GSH mostly intact, by specific transport systems, while in liver GSH uptake occurred only by its breakdown by γ-GT activity followed by intracellular resynthesis.

scholarly journals The Role of Ephrins-B1 and -B2 During Fetal Rat Lung Development

2015 ◽  
Vol 35 (1) ◽  
pp. 104-115 ◽  
Author(s):  
Francisca O. Peixoto ◽  
Patrícia Pereira-Terra ◽  
Rute S. Moura ◽  
Emanuel Carvalho-Dias ◽  
Jorge Correia-Pinto ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Lung Development ◽  
Fetal Lung ◽  
Cardiovascular Development ◽  
Rat Lung ◽  
Growth Promoters ◽  
Lung Morphogenesis ◽  
Rat Lungs ◽  
Fetal Rat

Background/ Aims: The knowledge of the molecular network that governs fetal lung branching is an essential step towards the discovery of novel therapeutic targets against pulmonary pathologies. Lung consists of two highly branched systems: airways and vasculature. Ephrins and its receptors, Eph, have been implicated in cardiovascular development, angiogenesis and vascular remodeling. This study aims to clarify the role of these factors during lung morphogenesis. Methods: Ephrins-B1, -B2 and receptor EphB4 expression pattern was assessed in fetal rat lungs between 15.5 and 21.5 days post-conception, by immunohistochemistry. Fetal rat lungs were harvested at 13.5 dpc, cultured during 4 days and treated with increasing doses of ephrins-B1 and -B2 and the activity of key signaling pathways was assessed. Results: Ephrin-B1 presents mesenchymal expression, whereas ephrin-B2 and its receptor EphB4 were expressed by the epithelium. Both ephrins stimulated pulmonary branching. Moreover, while ephrin-B1 did not affect the pathways studied, ephrin-B2 supplementation decreased activity of JNK, ERK and STAT. This study characterizes the expression pattern of ephrins-B1, -B2 and EphB4 receptor throughout rat lung development. Conclusion: Our data highlight a possible role of ephrins as molecular stimulators of lung morphogenesis. Moreover, it supports the idea that classical vascular factors might play a role as airway growth promoters.

Effects of separate and combined ETA and ETB blockade on ET-1-induced constriction in perfused rat lungs

1995 ◽  
Vol 269 (5) ◽  
pp. L668-L672 ◽  
Author(s):  
K. Sato ◽  
M. Oka ◽  
K. Hasunuma ◽  
M. Ohnishi ◽  
K. Sato ◽  
...  
Keyword(s):  
Pulmonary Edema ◽  
Vehicle Control ◽  
Receptor Blockade ◽  
Rat Lung ◽  
Pulmonary Vasoconstriction ◽  
Rat Lungs ◽  
Eta Receptor ◽  
Etb Receptor ◽  
Receptor Agonists And Antagonists

To evaluate the role of endothelin (ET) receptors in ET-1-induced pulmonary vasoreactivity, we studied the effects of ET-receptor agonists and antagonists in isolated perfused rat lungs. ET-1 (1-10 nM) caused concentration-dependent pulmonary vasoconstriction and gross pulmonary edema at a concentration of 10 nM. The combination of the selective ETA antagonist BQ-123 and the selective ETB antagonist BQ-788 inhibited ET-1-induced pulmonary vasoconstriction more effectively than BQ-123 alone, whereas BQ-788 alone enhanced the constriction. ET-1-induced hydrostatic pulmonary edema was prevented by the combination of BQ-123 and BQ-788 but not by either BQ-123 or BQ-788 alone. After the addition of 125 ng of exogenous ET-1, the perfusate levels of ET-1 were significantly higher in BQ-788-treated lungs than in either the vehicle control or BQ-123-treated lungs. The selective ETB agonist IRL-1620 also caused pulmonary vasoconstriction and edema, both of which were completely inhibited by BQ-788. ET-1-induced transient vasodilation was abolished by BQ-788 but was unaffected by BQ-123. These results suggest that in the isolated perfused rat lung, ET-1-induced vasoconstriction is mediated by both ETA and ETB receptors, whereas ET-1-induced transient vasodilation is mediated exclusively by the ETB receptor. Blockade of ETB receptors may result in enhanced ET-1 activity (via the ETA receptor) through inhibition of the ETB-mediated clearance of ET-1. Thus combined ETA and ETB blockade is required for the complete inhibition of ET-1-induced vasoconstriction in the rat pulmonary circulation.

The Leukocyte Digestion of Fibrinogen Degradation Products (FDP)

1971 ◽  
Vol 26 (03) ◽  
pp. 523-525
Author(s):  
K Gibiński ◽  
B Lipiński ◽  
M Trusz-Gluza
Keyword(s):  
Degradation Products ◽  
Fibrinogen Degradation Products

SummaryWhile the native fibrinogen is not digested by the leucocyte proteases both the early and late FDP are digestible without any denaturating reagent. Thus, this reaction may occur in vivo indicating an unknown role of granulocytes in paracoagulation.

Exercise-Induced Fibrinolysis – Fact or Fiction?

1982 ◽  
Vol 48 (02) ◽  
pp. 201-203 ◽  
Author(s):  
N A Marsh ◽  
P J Gaffney
Keyword(s):  
Plasminogen Activator ◽  
Degradation Products ◽  
Coagulation Factors ◽  
Vascular Wall ◽  
Strenuous Exercise ◽  
Fibrin Degradation Products ◽  
Real Increase ◽  
Exercise Induced ◽  
Male Subjects

SummaryThe effect of strenuous exercise on the fibrinolytic and coagulation mechanisms was examined in six healthy male subjects. Five min bicycle exercise at a work-rate of 800 to 1200 kpm. min−1 produced an abrupt increase in plasma plasminogen activator levels which disappeared after 90 min. However, there was no change in early or late fibrin degradation products nor was there a change in fibrinopeptide A levels or βthromboglobulin levels after exercise although activated partial thromboplastin times were significantly shortened. It is concluded that strenuous exercise does not produce any real increase in fibrinogen-fibrin conversion nor any real increase in the breakdown of these proteins. The role of exercise-induced release of plasminogen activator remains unclear, but probably helps to maintain plasma levels in a discontinuous manner concurrently with the continuous low-level secretion from the vascular wall. The shortening of partial thromboplastin time may be due to the raised levels of plasminogen activator changing the activation state of other coagulation factors.

scholarly journals Evaluating Targeted Therapies in Ovarian Cancer Metabolism: Novel Role for PCSK9 and Second Generation mTOR Inhibitors

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3727
Author(s):  
Dafne Jacome Sanz ◽  
Juuli Raivola ◽  
Hanna Karvonen ◽  
Mariliina Arjama ◽  
Harlan Barker ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Lipid Metabolism ◽  
Cell Survival ◽  
Drug Testing ◽  
Cancer Metabolism ◽  
Ex Vivo ◽  
Specific Inhibitor ◽  
Low Grade ◽  
Serous Ovarian Cancer

Background: Dysregulated lipid metabolism is emerging as a hallmark in several malignancies, including ovarian cancer (OC). Specifically, metastatic OC is highly dependent on lipid-rich omentum. We aimed to investigate the therapeutic value of targeting lipid metabolism in OC. For this purpose, we studied the role of PCSK9, a cholesterol-regulating enzyme, in OC cell survival and its downstream signaling. We also investigated the cytotoxic efficacy of a small library of metabolic (n = 11) and mTOR (n = 10) inhibitors using OC cell lines (n = 8) and ex vivo patient-derived cell cultures (PDCs, n = 5) to identify clinically suitable drug vulnerabilities. Targeting PCSK9 expression with siRNA or PCSK9 specific inhibitor (PF-06446846) impaired OC cell survival. In addition, overexpression of PCSK9 induced robust AKT phosphorylation along with increased expression of ERK1/2 and MEK1/2, suggesting a pro-survival role of PCSK9 in OC cells. Moreover, our drug testing revealed marked differences in cytotoxic responses to drugs targeting metabolic pathways of high-grade serous ovarian cancer (HGSOC) and low-grade serous ovarian cancer (LGSOC) PDCs. Our results show that targeting PCSK9 expression could impair OC cell survival, which warrants further investigation to address the dependency of this cancer on lipogenesis and omental metastasis. Moreover, the differences in metabolic gene expression and drug responses of OC PDCs indicate the existence of a metabolic heterogeneity within OC subtypes, which should be further explored for therapeutic improvements.

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