Phospholipids, prostaglandin E2, and proteolysis in denervated muscle

1986 ◽  
Vol 251 (1) ◽  
pp. R165-R173 ◽  
Author(s):  
J. Turinsky
Keyword(s):  
Protein Synthesis ◽  
Prostaglandin E2 ◽  
Pge2 Production ◽  
Nerve Transection ◽  
Denervated Muscle ◽  
Sciatic Nerve Transection ◽  
Tissue Protein ◽  
Pge2 Release ◽  
Denervated Muscles

Soleus muscles of rats were studied up to 16 days after sciatic nerve transection. At the end of this period the denervated soleus muscles exhibited decreased content of diphosphatidylglycerol (-44%), normal level of phosphatidylethanolamine, and increased contents of phosphatidylcholine (+24%), sphingomyelin (+48%), lysophosphatidylcholine (+110%), phosphatidylinositol (+37%), and phosphatidylserine (+40%) per milligram of tissue protein. In studies in vitro, prostaglandin E2 (PGE2) release and tyrosine release by denervated soleus muscles were 319 and 141%, respectively, greater than those of sham muscles. An almost complete inhibition of PGE2 release with 5 X 10(-4) M aspirin or 2.8 X 10(-6) M indomethacin had no effect on tyrosine release of sham muscles or the stimulated tyrosine release of the denervated muscles. Addition of 5 X 10(-5) M cycloheximide in the medium resulted in 63% inhibition of PGE2 release by both groups of muscles; concomitant absolute increments in tyrosine releases by denervated and sham muscles did not statistically differ. In the presence of both 5 X 10(-5) M cycloheximide and 5 X 10(-4) M aspirin in the medium, PGE2 production by denervated and sham muscles was inhibited 87% while tyrosine release of denervated muscles was 108% higher than that of sham animals. It is concluded that 1) atrophy of denervated soleus muscle is associated with stimulated activity of tissue phospholipase A2, increased production of prostaglandin E2, increased total proteolytic rate, and unchanged rate of protein synthesis; 2) acute inhibition of PGE2 production does not inhibit the stimulated proteolysis in denervated muscle; and 3) cycloheximide inhibits PGE2 production by muscle.

Prostaglandin E2 and muscle proteolysis: effect of burn injury and cycloheximide

1986 ◽  
Vol 250 (2) ◽  
pp. R207-R210
Author(s):  
C. J. McKinley ◽  
J. Turinsky
Keyword(s):  
Protein Synthesis ◽  
Arachidonic Acid ◽  
Prostaglandin E2 ◽  
Burn Injury ◽  
Pge2 Production ◽  
Limb Muscle ◽  
Tissue Protein ◽  
Pge2 Release ◽  
Tissue Protein Synthesis

Rats were subjected to a single hindlimb scald, and 3 days later soleus muscles from the burned and contralateral unburned hindlimbs were studied in vitro. Burned limb muscle released 354% more prostaglandin E2 (PGE2) and 119% more tyrosine than the contralateral uninjured counterpart. Neither the rate of net proteolysis in the uninjured muscle nor the stimulated net proteolysis in the burned limb muscle could be reduced by 90% inhibition of PGE2 production with aspirin or indomethacin. Inhibition of tissue protein synthesis with 5 X 10(-5) M cycloheximide stimulated tyrosine release by soleus muscles of both hindlimbs, but the increment in the burned limb muscle was 167% greater than in the contralateral uninjured counterpart. Concomitantly, cycloheximide decreased PGE2 releases by injured and uninjured muscles 90 and 73%, respectively. This previously unrecognized action of cycloheximide was investigated in soleus muscles of normal uninjured rats. It was found that 1 X 10(-6) M cycloheximide produces a 70% inhibition of muscle PGE2 release and increasing the concentration of inhibitor up to 500-fold does not further decrease PGE2 production. Cycloheximide acts by reducing the availability of endogenous arachidonic acid for PGE2 synthesis.

Modulation of prostaglandin E2 synthesis in rat skeletal muscle

1992 ◽  
Vol 262 (4) ◽  
pp. E476-E482 ◽  
Author(s):  
J. Turinsky ◽  
D. M. O'Sullivan ◽  
B. P. Bayly
Keyword(s):  
Protein Synthesis ◽  
Prostaglandin E2 ◽  
Muscle Denervation ◽  
Protein Synthesis Inhibitors ◽  
Rat Skeletal Muscle ◽  
Sham Control ◽  
Pge2 Release ◽  
Rat Soleus Muscle ◽  
Denervated Muscles

The effect of muscle denervation, inhibitors of protein synthesis, G proteins, and sphingolipids on prostaglandin E2 (PGE2) release by rat soleus muscle in vitro was investigated. To assess the effect of muscle denervation, the sciatic nerve in one hindlimb of rats was interrupted, and soleus muscles from the denervated hindlimb and the contralateral sham (control) hindlimb were excised 1-5 days after surgery. Compared with corresponding sham muscles, PGE2 release by denervated muscles was increased 56, 230, and 435% at 1, 3, and 5 days after denervation, respectively. Protein synthesis inhibitors cycloheximide (10 microM) and puromycin (10 microM) lowered PGE2 release by sham and denervated muscles 62-80%. The release of PGE2 by sham and denervated muscles was not altered by pertussis toxin (1 microgram/ml) but was inhibited 30-51% by AlF4-. Addition of 100 microM guanosine 5'-O-(3-thiotriphosphate) to saponin-permeabilized sham and denervated muscles had only a moderate, if any, stimulatory effect on PGE2 release. This effect was not counteracted by 1 mM guanosine 5'-O-(2-thiodiphosphate). Increasing muscle ceramide concentration by incubation with sphingomyelinase (100 mU/ml) increased PGE2 release by sham and denervated muscles 43 and 157%, respectively. Because degradation of ceramides yields sphingosine, the effect of sphingosine was also tested. Sphingosine (25 microM) increased PGE2 release by sham and denervated muscles 139 and 187%, respectively, without affecting muscle viability, as assessed by the release of lactate dehydrogenase. The data indicate that muscle denervation, treatment with sphingomyelinase, and sphingosine stimulate, whereas inhibitors of protein synthesis inhibit PGE2 synthesis by muscle.

scholarly journals Cyclic Mechanical Stretching Induces Autophagic Cell Death in Tenofibroblasts Through Activation of Prostaglandin E2 Production

2015 ◽  
Vol 36 (1) ◽  
pp. 24-33 ◽  
Author(s):  
Hua Chen ◽  
Liyang Chen ◽  
Biao Cheng ◽  
Chaoyin Jiang
Keyword(s):  
Cell Death ◽  
Prostaglandin E2 ◽  
Underlying Mechanism ◽  
Autophagic Cell Death ◽  
Pge2 Production ◽  
Dependent Manner ◽  
Small Interfering Rnas ◽  
Pge2 Release ◽  
Mechanical Stretching

Background/Aims: Autophagic cell death has recently been implicated in the pathophysiology of tendinopathy. Prostaglandin E2 (PGE2), a known inflammatory mediator of tendinitis, inhibits tenofibroblast proliferation in vitro; however, the underlying mechanism is unclear. The present study investigated the relationship between PGE2 production and autophagic cell death in mechanically loaded human patellar tendon fibroblasts (HPTFs) in vitro. Methods: Cultured HPTFs were subjected to exogenous PGE2 treatment or repetitive cyclic mechanical stretching. Cell death was determined by flow cytometry with acridine orange/ethidium bromide staining. Induction of autophagy was assessed by autophagy markers including the formation of autophagosomes and autolysosomes (by electron microscopy, AO staining, and formation of GPF-LC3-labeled vacuoles) and the expression of LC3-II and BECN1 (by western blot). Stretching-induced PGE2 release was determined by ELISA. Results: Exogenous PGE2 significantly induced cell death and autophagy in HPTFs in a dose-dependent manner. Blocking autophagy using inhibitors 3-methyladenine and chloroquine, or small interfering RNAs against autophagy genes Becn-1 and Atg-5 prevented PGE2-induced cell death. Cyclic mechanical stretching at 8% and 12% magnitudes for 24 h significantly stimulated PGE2 release by HPTFs in a magnitude-dependent manner. In addition, mechanical stretching induced autophagy and cell death. Blocking PGE2 production using COX inhibitors indomethacin and celecoxib significantly reduced stretching-induced autophagy and cell death. Conclusion: Taken together, cyclic mechanical stretching induces autophagic cell death in tenofibroblasts through activation of PGE2 production.

Neural regulation of the enhanced uptake of glucose in skeletal muscle after endotoxin

1995 ◽  
Vol 269 (2) ◽  
pp. R437-R444 ◽  
Author(s):  
C. H. Lang
Keyword(s):  
Skeletal Muscle ◽  
Nerve Transection ◽  
Muscle Denervation ◽  
Denervated Muscle ◽  
Muscle Type ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Sciatic Nerve Transection ◽  
Insulin Levels ◽  
Stimulation Of

Previous studies have demonstrated that in vivo injection of lipopolysaccharide (LPS) acutely stimulates glucose uptake (GU) in skeletal muscle. The purpose of the present study was to determine whether this enhanced GU is neurally mediated. In the first group of rats, a unilateral sciatic nerve transection was performed 3 h before injection of LPS, and in vivo GU was assessed using 2-[14C]deoxy-D-glucose 40 min after LPS injection. At this time, LPS-treated rats were hyperglycemic (12 mM), and insulin levels were not different from control rats. In the innervated leg, LPS increased GU 43-228%, depending on the muscle type. In contrast, LPS failed to increase GU in muscles from the denervated limb. In other experiments, somatostatin was infused to produce an insulinopenic condition before the injection of LPS. Despite insulinopenia, muscle GU was still increased by LPS. In control rats, in which the euglycemic hyperinsulinemic clamp technique was used, acute muscle denervation was shown to impair insulin-mediated GU in the presence of pharmacological, but not physiological, insulin levels. Non-insulin-mediated GU (NIMGU) was assessed in rats that were insulinopenic and hyperglycemic. In innervated muscle, NIMGU was increased 56-126 and 118-145% when the plasma glucose was elevated to 9 and 12 mM, respectively. In contrast, hyperglycemia-induced increases in NIMGU were attenuated in denervated muscle. These data demonstrate that 1) the early LPS-induced stimulation of muscle GU is mediated via a non-insulin-mediated pathway and 2) the LPS-induced increase in NIMGU in muscle is neurally mediated.

Tubular prostaglandin E2 production and its role in urinary hypotonicity after release of ureteral occlusion in the rat

1987 ◽  
Vol 73 (4) ◽  
pp. 395-399 ◽  
Author(s):  
Shozo Torikai
Keyword(s):  
Prostaglandin E2 ◽  
Collecting Duct ◽  
Urine Osmolality ◽  
Urine Concentration ◽  
Pge2 Production ◽  
Endogenous Prostaglandin ◽  
Collecting Ducts ◽  
Ureteral Occlusion

1. In order to explore the involvement of endogenous prostaglandin E2 (PGE2) in the urine concentration defect after ureteral occlusion, PGE2 production by isolated collecting ducts in vitro and effects of indomethacin on urine osmolality in vivo were examined. 2. Twenty-four hours ureter obstruction caused increased PGE2 production by the medullary collecting ducts, which was maintained at a high level on the day after release of obstruction (0.8 ± 0.2 pg/mm normal, 8.1 ± 0.9 pg/mm 24 h obstruction, and 6.6 ± 1.0 pg/mm post-obstruction, mean ± sem). An enhanced PGE2 production was also observed for papillary collecting duct on the day after release of 24 h ureteral occlusion (3.9 ± 0.5 pg/mm normal and 7.7 ± 1.2 pg/mm post-obstruction). 3. Administration of indomethacin to the unilateral post-obstructive rats slightly raised the urine osmolality of the post-obstructed kidney (from 339 ± 17 to 390 ± 22 mosmol/kg H2O), while it had a greater effect on the contralateral intact kidney (from 1569 ± 138 to 2567 ± 198 mosmol/kg H2O). 4. Our data may indicate that the urine concentration defect after 24 h ureteral occlusion is ascribable mainly to a mechanism other than increased endogenous PGE2.

scholarly journals The influence of passive stretch on the growth and protein turnover of the denervated extensor digitorum longus muscle

1978 ◽  
Vol 174 (2) ◽  
pp. 595-602 ◽  
Author(s):  
David F. Goldspink
Keyword(s):  
Protein Synthesis ◽  
Extensor Digitorum Longus ◽  
Similar Rate ◽  
Extensor Digitorum Longus Muscle ◽  
Extensor Digitorum ◽  
Denervated Muscle ◽  
Longus Muscle ◽  
Induced Changes ◽  
Passive Stretch

At 7 days after cutting the sciatic nerve, the extensor digitorum longus muscle was smaller and contained less protein than its innervated control. Correlating with these changes was the finding of elevated rates of protein degradation (measured in vitro) in the denervated tissue. However, at this time, rates of protein synthesis (measured in vitro) and nucleic acid concentrations were also higher in the denervated tissue, changes more usually associated with an active muscle rather than a disused one. These anabolic trends have, at least in part, been explained by the possible greater exposure of the denervated extensor digitorum longus to passive stretch. When immobilized under a maintained influence of stretch the denervated muscle grew to a greater extent. Although this stretch-induced growth appeared to occur predominantly through a stimulation of protein synthesis, it was opposed by smaller increases in degradative rates. Nucleic acids increased at a similar rate to the increase in muscle mass when a continuous influence of stretch was imposed on the denervated tissue. In contrast, immobilization of the denervated extensor digitorum longus in a shortened unstretched state reversed most of the stretch-induced changes; that is, the muscle became even smaller, with protein synthesis decreasing to a greater extent than breakdown after the removal of passive stretch. The present investigation suggests that stretch will promote protein synthesis and hence growth of the extensor digitorum longus even in the absence of an intact nerve supply. However, some factor(s), in addition to passive stretch, must contribute to the anabolic trends in this denervated muscle.

Effects of atrial natriuretic peptide on renal medullary prostaglandin E2 production

1989 ◽  
Vol 257 (3) ◽  
pp. F336-F340
Author(s):  
R. J. Bolterman ◽  
M. D. Bentley ◽  
S. M. Sandberg ◽  
M. J. Fiksen-Olsen ◽  
J. C. Romero
Keyword(s):  
Arachidonic Acid ◽  
Atrial Natriuretic Peptide ◽  
Prostaglandin E2 ◽  
Natriuretic Peptide ◽  
Inhibitory Effect ◽  
Pge2 Production ◽  
In Vitro Effects ◽  
Different Doses ◽  
Atrial Natriuretic

Like arachidonic acid (AA) and bradykinin (BK), the intrarenal administration of atrial natriuretic peptide (ANP) has been shown to increase the urinary excretion of prostaglandin E2 (PGE2). In the present study, the direct in vitro effects of ANP on PGE2 production were compared with those of AA and BK. Canine renal inner medullary slices were preincubated for 30 min and washed in aerated Krebs-Ringer buffer (37 degrees C). During the final incubation period, with the use of varied concentrations of AA, BK, or ANP in Krebs-Ringer buffer, samples were obtained at 0 and 30 min to be used for radioimmunoassay of PGE2. Although the rate of PGE2 production was significantly increased 11-fold with AA and threefold with BK, it was unaffected by four different doses of ANP (10(-5) to 10(-11) M). Furthermore, the production of PGE2 during basal and stimulated (BK or AA) conditions was significantly blocked by indomethacin but not by ANP. These results indicate that ANP had no direct stimulatory or inhibitory effect on the medullary production of PGE2.

scholarly journals Interleukin-12 (IL-12) Production in Whole Blood Cultures From Human Immunodeficiency Virus-Infected Individuals Studied in Relation to IL-10 and Prostaglandin E2 Production

Blood ◽  
1997 ◽  
Vol 89 (2) ◽  
pp. 570-576 ◽  
Author(s):  
Linde Meyaard ◽  
Egbert Hovenkamp ◽  
Nadine Pakker ◽  
Tineke C.T.M. van der Pouw Kraan ◽  
Frank Miedema
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Prostaglandin E2 ◽  
Whole Blood ◽  
Peripheral Blood ◽  
Blood Cultures ◽  
Pge2 Production ◽  
Interleukin 12 ◽  
Immunodeficiency Virus

Abstract The role of interleukin-12 (IL-12) in Th1 cell differentiation is well established. The heterodimer p70, composed of a p40 and a p35 chain, is the biologically active form. IL-12 production by human monocytes is enhanced by interferon-γ (IFN-γ) and inhibited by IL-10 and prostaglandin E2 (PGE2 ). Peripheral blood mononuclear cells from human immunodeficiency virus (HIV)-infected individuals reportedly have impaired IL-12 p40 and p70 production on stimulation with Staphylococcus aureus Cowan I (SAC) in vitro. Both PGE2 and IL-10 previously were proposed to be instrumental in this defect in IL-12 production. Here, we studied IL-12 p40 and p70 production in relation to IL-10 and PGE2 production in whole blood cultures from HIV-infected individuals. On stimulation with lipopolysaccharide, IL-12 production was normal. However, on stimulation with SAC, IL-12 p40 and p70 production was decreased in HIV-infected individuals and correlated significantly with decreased peripheral blood CD4+ T-cell number and T-cell reactivity to CD3 monoclonal antibody in vitro. However, IL-10 and PGE2 production in cultures from HIV-infected individuals was normal and did not relate to IL-12 production. In conclusion, IL-12 production by cells from HIV-infected individuals is impaired under certain conditions in vitro and this decrease is independent of IL-10 or PGE2 production.

Synthesis of prostaglandin E2 in different segments of isolated collecting tubules from adult and neonatal rabbits

1985 ◽  
Vol 248 (1) ◽  
pp. F134-F144 ◽  
Author(s):  
D. Schlondorff ◽  
J. A. Satriano ◽  
G. J. Schwartz
Keyword(s):  
Arachidonic Acid ◽  
Prostaglandin E2 ◽  
Feedback Loop ◽  
Pge2 Production ◽  
Large Variability ◽  
Pge2 Synthesis ◽  
Collecting Tubule ◽  
Concentrate Urine ◽  
Collecting Tubules

Prostaglandin E2 (PGE2) inhibits the action of the antidiuretic hormone (ADH) in isolated collecting tubules. A negative feedback loop has been postulated whereby ADH stimulates PGE2 synthesis. Furthermore, lysyl-bradykinin (LBK) inhibits the antidiuretic effect of ADH, probably via PGE2. Enhanced PGE2 synthesis has also been implicated as contributing to the inability to maximally concentrate urine during the neonatal period. We investigated PGE2 synthesis in microdissected cortical (CCT), medullary (MCT), and branched cortical (BCT) collecting tubules from adult and in corticomedullary collecting tubules (CT) from newborn rabbits. Isolated BCT produced significantly less PGE2 (12 +/- 2 pg X mm-1 X 20 min-1) than CCT (65 +/- 9) or MCT (76 +/- 8) from kidneys of adult rabbits. CT from newborn rabbits produced only 19 +/- 3 pg/mm, significantly less than either CCT or MCT from adults. A large variability in basal PGE2 production and hormonal response was observed from tubule to tubule. Under either basal conditions or in the presence of 2 microM arachidonic acid, LBK enhanced PGE2 synthesis in CCT and MCT from adults. ADH enhanced PGE2 production in MCT under basal conditions and in CCT in the presence of arachidonic acid. Neither LBK nor ADH stimulated PGE2 synthesis in neonatal CT. A23187 consistently stimulated PGE2 synthesis in CCT and MCT from adults and, to a lesser extent, in CT from newborn rabbits. Our results support the hypothesis that ADH and LBK enhance PGE2 synthesis in the collecting tubule. This response is, however, subject to large variations from tubule to tubule and depends on the in vitro incubation conditions.

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