Effect of FTY720P on lipid accumulation in HEPG2 cells.

Nonalcoholic fatty liver disease (NAFLD) is characterized by an increase in hepatic lipid accumulation due to impaired lipid metabolism. Although a correlation was found between NAFLD and sphingosine-1-phosphate (S1P), the role of the sphingolipid remains controversial. The aim of this study was to investigate any involvement of S1P in steatosis using its analog FTY720P and HepG2 cells.

Identified and potential internalization signals involved in trafficking and regulation of Na/K ATPase activity.

The sodium-potassium pump (NKA) or Na/K ATPase consumes around 30-40% of the total energy expenditure of the animal cell on the generation of the sodium and potassium electrochemical gradients that regulate various electrolyte and nutrient transport processes. The vital role of this protein entails proper spatial and temporal regulation of its activity through modulatory mechanisms involving its expression, localization, enzymatic activity, and protein-protein interactions. The residence of the NKA at the plasma membrane is compulsory for its action as an antiporter.

Signaling Cascade Mediating the Effect of FTY720P on the Na/K ATPase in LLC-PK1.

Background/aims: In renal ischemia, the Na/K ATPase of the kidney epithelial cells translocates to intracellular compartments, resulting in altered kidney functions. Sphingosine-1-phosphate (S1P) was shown to play a protective role against this ischemic injury. Whether the sphingolipid targets the Na/K ATPase is a possibility that has not been explored before.

Adverse effect of FTY720P on colonic Na /K ATPase is mediated via ERK, p38MAPK, PKC, and PI3K.

FTY720P, an analogue of sphingosine 1-phosphate, has emerged lately as a potential causative agent of inflammatory bowel disease, in which electrolytes movements driven by the sodium gradient established by the Na /K ATPase are altered. We showed previously in Caco-2 cells, a 50% FTY720P-induced decrease in the ATPase activity, mediated via S1PR2 and PGE2. This work aims at delineating the mechanism underlying PGE2 release and at investigating if the ATPase inhibition is due to changes in its abundance.

Cow's milk may be delivering potentially harmful undetected cargoes to humans. Is it time to reconsider dairy recommendations?

Mammalian evolution has shaped milk into a species-specific vehicle for post-natal development, continuing what began within the mother's womb. Increased consumption of the mother's breast milk is associated with the most adequate metabolic programming and lowers the incidence of the diseases of civilization during adulthood. An abundance of short sequences of RNA, known as microRNA, exists in mammalian breast milk, enclosed within robust small extracellular vesicles known as exosomes.

PGE2 upregulates the Na+/K+ ATPase in HepG2 cells via EP4 receptors and intracellular calcium.

The Na+/K+ ATPase is a key regulator of the hepatocytes ionic homeostasis, which when altered may lead to many liver disorders. We demonstrated recently, a significant stimulation of the Na+/K+ ATPase in HepG2 cells treated with the S1P analogue FTY 720P, that was mediated through PGE2. The mechanism by which the prostaglandin exerts its effect was not investigated, and is the focus of this work.

FTY720P Upregulates the Na+/K+ ATPase in HepG2 Cells by Activating S1PR3 and Inducing PGE2 Release.

Background/aims: Liver regeneration is induced by S1P and accompanied with an increase in hepatic Na/K ATPase activity, suggesting a potential modulatory role of the sphingolipid on the ATPase activity. The ability of S1P to alter the ATPase activity was confirmed in a previous work which showed a time dependent effect, with an inhibition appearing at 15min and a stimulation at two hours. The aim of this work was to investigate if FTY720-P, an analogue of S1P used in the treatment of multiple sclerosis, exerts a similar effect at 2 hours.

The epinephrine-induced PGE2 reduces Na+/K+ ATPase activity in Caco-2 cells via PKC, NF-κB and NO.

We showed previously an epinephrine-induced inhibition of the Na+/K+ ATPase in Caco-2 cells mediated via PGE2. This work is an attempt to further elucidate mediators downstream of PGE2 and involved in the observed inhibitory effect. The activity of the Na+/K+ ATPase was assayed by measuring the amount of inorganic phosphate liberated in presence and absence of ouabain, a specific inhibitor of the enzyme.

FTY720P inhibits the Na/K ATPase in Caco-2 cells via S1PR2: PGE2 and NO are along the signaling pathway.

Aims: Sphingosine-1-phosphate (S1P) has been implicated lately in inflammatory bowel disease which has diarrhea as one of its symptoms. Diarrhea is due to altered water movements as a result of altered electrolyte transport, and in particular sodium. Sodium movements are geared by the sodium gradient established by the Na/K ATPase.

Epinephrine modulates Na+/K+ ATPase activity in Caco-2 cells via Src, p38MAPK, ERK and PGE2.

Epinephrine, a key stress hormone, is known to affect ion transport in the colon. Stress has been associated with alterations in colonic functions leading to changes in water movements manifested as diarrhea or constipation. Colonic water movement is driven by the Na+-gradient created by the Na+/K+-ATPase.

Signaling pathway involved in the inhibitory effect of FTY720P on the Na/K ATPase in HepG2 cells.

The Na/K ATPase modulates the activity of many transporters in the liver, and maintains the ionic constancy of the intracellular milieu, preserving thus normal functioning of hepatocytes. Previous work showed that FTY720P, a sphingosine one phosphate receptor agonist used in the treatment of multiple sclerosis, exerts in HepG2 cells, an inhibitory effect on the activity of the ATPase, mediated via PGE2. This study is an attempt to identify the signaling molecules involved downstream of the prostaglandin.

FTY720P inhibits hepatic Na(+)-K(+) ATPase via S1PR2 and PGE2.

Sphingosine-1-phosphate (S1P) was found previously to inhibit Na(+)-K(+) ATPase in HepG2 cells. Whether fingolimod (FTY720), a S1P receptor (S1PR) agonist, similarly inhibits the ATPase is a question that needs to be addressed. The aim of this work was to study the effect of FTY720P, the active form of the drug, on the activity of Na(+)-K(+) ATPase in HepG2 cells and determine its mechanism of action.

The Appearance of a Leptin Effect on Glucose Absorption in Caco2 Cells Depends on Their Differentiation Level.

Unlabelled: Backdround/Aims: The aim of this work was to study the effect and mechanism of action of leptin added apically, on glucose absorption, using Caco-2 cells as a model.

Methods: Cells were grown on inserts and treated with leptin, at different time points after confluence. Radiolabelled glucose was added to the upper chamber and samples from the lower chamber were collected and assayed for radioactivity.

Leptin inhibits the Na(+)/K(+) ATPase in Caco-2 cells via PKC and p38MAPK.

We demonstrated previously an inhibitory effect of luminal leptin on glucose absorption in differentiated Caco-2 cells. Since this process is dependent on the Na(+) gradient established by the Na(+)/K(+)ATPase this work was undertaken to investigate if the ATPase is one of the hormone's targets. Fully differentiated Caco-2 cells were incubated with 10nM luminal leptin and the activity of the Na(+)/K(+) ATPase was assayed by measuring the amount of inorganic phosphate liberated.

Ceramide and its metabolites modulate time-dependently the activity of the Na⁺/K⁺ ATPase in HepG2 cells.

Ceramide is involved in the regulation of many cellular processes including cell proliferation and apoptosis, which are accompanied respectively with a decrease and an increase in the activity of the Na(+)/K(+) ATPase. These antagonistic effects may be time-dependent and due to different signaling pathways requiring different time intervals to be activated. While we showed previously a ceramide-induced inhibition of the ATPase in HepG2 cells during the first hour, we study here the effect of ceramide thereafter.

Anti-hyperglycemic effect of the aqueous extract of banana infructescence stalks in streptozotocin-induced diabetic rats.

Water extract of banana (Musa sapientum) infructescence stalks has been used in folk medicine in the treatment of diabetes mellitus. This work aims at verifying the claimed effect and elucidating its possible mode of action. The extract was given in replacement of drinking water to diabetic rats, and its mechanism of action was studied by investigating its involvement in glucose transport in Caco-2 monolayers, and in rat jejuna using an in situ perfusion technique.

Sphingosine-1-phosphate is a mediator of TNF-α action on the Na+/K+ ATPase in HepG2 cells.

We showed previously that TNF-α down-regulates the Na+/K+ ATPase in HepG2 cells. This work was undertaken to study the role of ceramide and its metabolites in TNF-α action. Treating HepG2 cells with the cytokine in presence of an inhibitor of sphingomyelinase, abrogated the effect of TNF-α on the ATPase.

Insulin targets the Na(+)/K(+) ATPase in enterocytes via PI3K, PKC, and MAPKS.

The effect of insulin on intestinal Na(+)/K(+) ATPase is till now undetermined, and it is still unclear whether insulin exerts any modulatory effect on glucose absorption by targeting the ATPase. This work attempted to address this question and to unravel the signaling pathway involved using Caco-2 cells as a model. After an overnight starvation, cells were treated with insulin in presence and absence of specific inhibitors of some known mediators.

Pine bark extract inhibits glucose transport in enterocytes via mitogen-activated kinase and phosphoinositol 3-kinase.

Objective: Pine bark extract (PBE) has been reported to have hypoglycemic effects but its mode of action is still unclear. This work studied the effect of PBE on glucose uptake by Caco-2 cells in isolation of its effect on insulin, which may appear if ingested by the animal.

Methods: Caco-2 cells were incubated in the presence of PBE and [(14)C] 3-O-methyl-D-glucose as a tracer and the change in radioactivity of the incubation medium was taken as a measurement of glucose uptake.

Insulin down-regulates the Na+/K+ ATPase in enterocytes but increases intestinal glucose absorption.

The effect of insulin on [(14)C] 3-O-methyl-d-glucose (3OMG) absorption in the rat jejunum was studied using an in situ perfusion technique. Insulin increased apical glucose entry into the cells and decreased intestinal retention suggesting that serosal glucose transport was enhanced by the hormone. This enhanced uptake was ascribed to an increase in the expression of glucose transporters as confirmed by Western blot analysis and not to a higher sodium gradient, since insulin reduced the activity and protein expression of the Na(+)/K(+) ATPase.

TNF-alpha reduces the Na+/K+ ATPase activity in LLC-PK1 cells by activating caspases and JNK and inhibiting NF-kappaB.

TNF-alpha has recently been implicated in diabetic nephropathy, which is usually accompanied by higher sodium retention. The kidneys play a major role in sodium homeostasis by regulating tubular sodium reabsorption, a process geared by the sodium gradient established by the Na(+)/K(+) ATPase. The aim of this work was to investigate the effect of TNF on the ATPase, and consequently its implication in kidney malfunction, using LLC-PK1 cells.

Signaling pathway underlying the up-regulatory effect of TNF-alpha on the Na(+)/K(+) ATPase in HepG2 cells.

The activity of the Na(+)/K(+) ATPase was shown to be reduced during apoptosis and enhanced during cell proliferation. This work investigated whether TNF-alpha exerts also opposite effects on the Na(+)/K(+) ATPase in HepG2 cells and whether these effects are time-dependent. A time response study demonstrated that the activity and protein expression of the ATPase are decreased at 1h and increased at 4, 6 and 8h.

Linalool decreases HepG2 viability by inhibiting mitochondrial complexes I and II, increasing reactive oxygen species and decreasing ATP and GSH levels.

Coriander is used as an appetizer, a common food seasoning in Mediterranean dishes, and a remedy for many ailments. In this study we tested the biochemical effect of its essential oil components, in particular linalool, its main component. The oil extract was prepared by hydro-distillation of coriander seeds.

JNK modulates the effect of caspases and NF-kappaB in the TNF-alpha-induced down-regulation of Na+/K+ATPase in HepG2 cells.

An inhibition of the Na(+)/K(+)ATPase was previously shown to accompany and potentiate apoptosis in different experimental models. Since TNF-alpha is known to be a pro and anti-apoptotic cytokine, this work was undertaken to study the effect of TNF-alpha on the Na(+)/K(+)ATPase in HepG2 cells and to determine the signaling pathway involved. Cells were incubated for 1 h with TNF-alpha in presence and absence of PDTC, SP600125 and FK009, respective inhibitors of NF-KB, c-JNK, and caspases.