Calcium-independent inhibition of glucose transport in PC-12 and L6 cells by calcium channel antagonists

2002 ◽  
Vol 283 (2) ◽  
pp. C579-C586 ◽  
Author(s):  
Timothy D. Ardizzone ◽  
Xiao-Hong Lu ◽  
Donard S. Dwyer
Keyword(s):  
Calcium Channel ◽  
Glucose Transport ◽  
Cell Model ◽  
Neuronal Cell ◽  
Dependent Manner ◽  
Calcium Channel Antagonists ◽  
A Cell ◽  
Uptake Medium ◽  
L6 Muscle Cells ◽  
Dose Dependent

The goal of these studies was to determine whether different calcium channel antagonists affect glucose transport in a neuronal cell line. Rat pheochromocytoma (PC-12) cells were treated with L-, T-, and N-type calcium channel antagonists before measurement of accumulation of 2-[3H]deoxyglucose (2-[3H]DG). The L-type channel antagonists nimodipine, nifedipine, verapamil, and diltiazem all inhibited glucose transport in a dose-dependent manner (2–150 μM) with nimodipine being the most potent and diltiazem only moderately inhibiting transport. T- and N-type channel antagonists had no effect on transport. The L-type channel agonist l-BAY K 8644 also inhibited uptake of 2-[3H]DG. The ability of these drugs to inhibit glucose transport was significantly diminished by the presence of unlabeled 2-DG in the uptake medium. Some experiments were performed in the presence of EDTA (4 mM) or in uptake buffer without calcium. The absence of calcium in the uptake medium had no effect on inhibition of glucose transport by nimodipine or verapamil. To examine the effects of these drugs on a cell model of a peripheral tissue, we studied rat L6 muscle cells. The drugs inhibited glucose transport in L6 myoblasts in a dose-dependent manner that was independent of calcium in the uptake medium. These studies suggest that the calcium channel antagonists inhibit glucose transport in cells through mechanisms other than the antagonism of calcium channels, perhaps by acting directly on glucose transporters.

Diverse effects of calcium channel blockers on skeletal muscle glucose transport

1992 ◽  
Vol 263 (1) ◽  
pp. R70-R75 ◽  
Author(s):  
G. D. Cartee ◽  
C. Briggs-Tung ◽  
J. O. Holloszy
Keyword(s):  
Skeletal Muscle ◽  
Calcium Channel ◽  
Glucose Transport ◽  
Channel Blocker ◽  
Transport Rate ◽  
Optical Isomers ◽  
Channel Blockers ◽  
Dependent Manner ◽  
Muscle Glucose Transport ◽  
Dose Dependent

Verapamil, a calcium channel blocker, inhibited the insulin-stimulated glucose transport rate in isolated rat epitrochlearis muscle in a dose-dependent manner (1-200 microM) without affecting basal glucose transport rate. Verapamil's inhibition was rapid in onset and disappearance; changes in glucose transport rate were detectable when verapamil was added to or removed from the incubation medium 15 min prior to measurement of glucose transport. Verapamil also inhibited the stimulation of muscle glucose transport caused by hypoxia, indicating that the effect was not limited to insulin action. Although the optical isomers of verapamil vary considerably in their potency as Ca2+ channel blockers, they were equally effective inhibitors of insulin-stimulated glucose transport rate. Nifedipine (10-200 microM), a more potent blocker of skeletal muscle Ca2+ channels than verapamil, was less effective as an inhibitor of insulin-stimulated glucose transport. Furthermore, nifedipine (10 microM) did not inhibit hypoxia-stimulated glucose transport. Diltiazem (200 microM), another Ca2+ channel blocker, did not reduce insulin-stimulated glucose transport.

scholarly journals PapRIV, a BV-2 microglial cell activating quorum sensing peptide

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yorick Janssens ◽  
Nathan Debunne ◽  
Anton De Spiegeleer ◽  
Evelien Wynendaele ◽  
Marta Planas ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Cell Model ◽  
Dependent Manner ◽  
Communication Signals ◽  
Gram Positive Bacteria ◽  
A Cell ◽  
Gastro Intestinal Tract

AbstractQuorum sensing peptides (QSPs) are bacterial peptides produced by Gram-positive bacteria to communicate with their peers in a cell-density dependent manner. These peptides do not only act as interbacterial communication signals, but can also have effects on the host. Compelling evidence demonstrates the presence of a gut-brain axis and more specifically, the role of the gut microbiota in microglial functioning. The aim of this study is to investigate microglial activating properties of a selected QSP (PapRIV) which is produced by Bacillus cereus species. PapRIV showed in vitro activating properties of BV-2 microglia cells and was able to cross the in vitro Caco-2 cell model and reach the brain. In vivo peptide presence was also demonstrated in mouse plasma. The peptide caused induction of IL-6, TNFα and ROS expression and increased the fraction of ameboid BV-2 microglia cells in an NF-κB dependent manner. Different metabolites were identified in serum, of which the main metabolite still remained active. PapRIV is thus able to cross the gastro-intestinal tract and the blood–brain barrier and shows in vitro activating properties in BV-2 microglia cells, hereby indicating a potential role of this quorum sensing peptide in gut-brain interaction.

Detection of α1 Integrin in Urine of Patients With Immunoglobulin A Nephropathy

2008 ◽  
Vol 56 (3) ◽  
pp. 581-586
Author(s):  
Jonathan Bank ◽  
Aharon Ben-David ◽  
Ram Doolman ◽  
Ben-Ami Sela ◽  
Ilan Bank
Keyword(s):  
Mesangial Cells ◽  
Kidney Diseases ◽  
Surface Membrane ◽  
Immunoglobulin A ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Healthy Individuals ◽  
Immunoglobulin A Nephropathy ◽  
A Cell ◽  
Dose Dependent

BackgroundThe α1β1 integrin is a cell surface membrane heterodimer composed of noncovalently linked α1 and β1 polypeptides that is up-regulated on activated and proliferating mesangial cells.MethodsA double-sandwich enzyme-linked immunosorbent assay that detects α1 integrin in a specific and dose-dependent manner at concentrations greater than 150 ng/mL was used to evaluate whether intact α1 polypeptides are secreted in the urine samples of 29 patients with various kidney diseases and in those of 5 healthy individuals.Resultsα1 Integrin was detected in 8 of the 29 patients including 3 of 3 patients with biopsy-proven immunoglobulin A nephropathy and 3 of 3 clinically suspected but non-biopsy-proven immunoglobulin A nephropathy with evidence of active nephritis. No α1 integrins were found in samples of 5 healthy controls.Conclusionsα1 Integrin polypeptides can be detected in human urine, particularly in immunoglobulin A nephropathy. Further extensive studies are required to clarify the significance of secretion of α1 integrins in urine of patients with kidney disease.

scholarly journals Vitamin A and bone formation. Effect of an excess of retinol on bone collagen synthesis in vitro

1985 ◽  
Vol 226 (3) ◽  
pp. 789-795 ◽  
Author(s):  
I Dickson ◽  
J Walls
Keyword(s):  
Bone Formation ◽  
Collagen Synthesis ◽  
Bone Collagen ◽  
Dependent Manner ◽  
Stimulate Bone Resorption ◽  
Dna And Rna ◽  
A Cell ◽  
Dose Dependent ◽  
Bone Collagen Synthesis

The influence of an excess of retinol on bone formation was studied by using cultures of embryonic-chick calvaria. Retinol decreased collagen synthesis in a dose-dependent manner, non-collagenous protein synthesis being relatively unaffected. Collagen synthesis was significantly inhibited after 24 h of culture with retinol and was progressively decreased, compared with control cultures containing no retinol, as the period of culture was increased. The effect of retinol on collagen synthesis could be reversed by incubation of calvaria for further periods in retinol-free medium. Incorporation of [3H]thymidine and [3H]uridine into DNA and RNA respectively was not altered by culturing calvaria with retinol for 22 h. These latter findings, and the selectivity for collagen synthesis, all suggested that the effect observed was not a cell-toxicity phenomenon. The effect of retinol on collagen synthesis by chick calvarial osteoblasts was probably direct and not mediated by osteoclasts, since a negligible number of the latter cells is present in chick calvaria. In cultures of neonatal murine calvaria, which contain many osteoclasts, retinol similarly inhibited synthesis of collagen, but not of non-collagenous protein; the concentrations of retinol necessary to produce the response were similar to those required to stimulate bone resorption in vitro.

scholarly journals ROS-Induced GATA4 and GATA6 Downregulation Inhibits StAR Expression in LPS-Treated Porcine Granulosa-Lutein Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Xiaolu Qu ◽  
Leyan Yan ◽  
Rihong Guo ◽  
Hui Li ◽  
Zhendan Shi
Keyword(s):  
Molecular Mechanisms ◽  
Cell Model ◽  
Animal Husbandry ◽  
Dependent Manner ◽  
Progesterone Production ◽  
Progesterone Synthesis ◽  
Porcine Granulosa Cell ◽  
Underlying Mechanisms ◽  
Dose Dependent

LPS is a major endotoxin produced by gram-negative bacteria, and exposure to it commonly occurs in animal husbandry. Previous studies have shown that LPS infection disturbs steroidogenesis, including progesterone production, and subsequently decreases animal reproductive performance. However, little information about the underlying mechanisms is available thus far. In the present study, an in vitro-luteinized porcine granulosa cell model was used to study the underlying molecular mechanisms of LPS treatment. We found that LPS significantly inhibits progesterone production and downregulates the expressions of progesterone synthesis-associated genes (StAR, CYP11A1, and 3β-HSD). Furthermore, the levels of ROS were significantly increased in an LPS dose-dependent manner. Moreover, transcriptional factors GATA4 and GATA6, but not NR5A1, were significantly downregulated. Elimination of LPS-stimulated ROS by melatonin or vitamin C could restore the expressions of GATA4, GATA6, and StAR. In parallel, StAR expression was also inhibited by the knockdown of GATA4 and GATA6. Based on these data, we conclude that LPS impairs StAR expression via the ROS-induced downregulation of GATA4 and GATA6. Collectively, these findings provide new insights into the understanding of reproductive losses in animals suffering from bacterial infection and LPS exposure.

scholarly journals Interferons and Ribavirin Effectively Inhibit Norwalk Virus Replication in Replicon-Bearing Cells

2007 ◽  
Vol 81 (22) ◽  
pp. 12111-12118 ◽  
Author(s):  
Kyeong-Ok Chang ◽  
David W. George
Keyword(s):  
Mutation Rates ◽  
Sequencing Analysis ◽  
Dependent Manner ◽  
Cell Culture System ◽  
Norwalk Virus ◽  
Antiviral Effects ◽  
A Cell ◽  
Ifn Γ ◽  
Dose Dependent ◽  
Excellent Tool

ABSTRACT The development of effective therapies for noroviral gastroenteritis has been hampered by the absence of a cell culture system. Recently, we reported the generation of Norwalk virus (NV) replicon-bearing cells in BHK21 and Huh-7 cells and demonstrated that alpha interferon (IFN-α) effectively inhibited the replication of NV in these cells. In continuing studies for screening potential antinoroviral agents, we tested IFN-γ and ribavirin for their effects on NV replication in the cells. Like IFN-α, IFN-γ inhibited the replication of NV in the replicon-bearing cells, showing the reduction of the NV genome and proteins in a dose-dependent manner. The effective dose for reducing 50% (ED50) of the NV genome and protein was calculated to be approximately 40 units/ml. When ribavirin was applied to the cells, it effectively reduced the NV genome and protein with the ED50 calculated as approximately 40 μM. The combination of IFN-α and ribavirin showed additive effects on the inhibition of NV replication. With the addition of guanosine to the ribavirin treatment, moderately reversed antiviral effects were observed, suggesting that the ribavirin effect may be associated with the depletion of GTP in the cells. Sequencing analysis of the conserved polymerase regions of NV in the ribavirin-treated (100 μM) and nontreated groups showed that the mutation rates were similar and indicated that ribavirin did not induce catastrophic mutations. The NV replicon-bearing cells provide an excellent tool for screening potential antinoroviral agents, and our results indicated that IFNs and ribavirin may be good therapeutic options for noroviral gastroenteritis.

scholarly journals FGF21 Ameliorates Hepatic Fibrosis by Multiple Mechanisms

2021 ◽  
Author(s):  
Fanrui Meng ◽  
Mir Hassan Khoso ◽  
Kai Kang ◽  
Qi He ◽  
Yukai Cao ◽  
...  
Keyword(s):  
Protein Expression ◽  
Western Blot ◽  
Hepatic Fibrosis ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Cell Model ◽  
Dependent Manner ◽  
Rt Pcr ◽  
Mrna And Protein Expression ◽  
Dose Dependent

Abstract Previous study reports that FGF21 could ameliorate hepatic fibrosis, but its mechanisms have not been fully investigated. In this study, three models were used to investigate the mechanism by which FGF21 alleviates liver fibrosis. CCL4 and DMN were respectively used to induce hepatic fibrosis animal models. Our results demonstrated that liver index and liver function were deteriorated in both models. HE and Masson’s staining showed that the damaged tissue architectonics were observed in the mice of both models. Treatment with FGF21 significantly ameliorated these changes. ELISA analysis showed that the serum levels of IL-1β, IL-6 and TNF-α were significantly elevated in both models. However, administration of FGF21 significantly reduced these inflammatory cytokines. RT-PCR and Western blot analysis showed that mRNA and protein expression of collagenI, α-SMA and TGF-β were significantly decreased by treatment with FGF21. PDGF-BB stimulant was used to establish the experimental cell model in HSCs. RT-PCR and Western blot analysis demonstrated that the expression of collagenI and α-SMA were significantly upregulated by this stimulant in model group. Interestingly, our results showed that mRNA and protein expression of leptin were also significantly induced in PDGF-BB treated HSCs. Administration of FGF21 could significantly reduce leptin expression in a dose dependent manner and these effects were reversed in siRNA (against β-klotho) transfected HSCs. Furthermore, the leptin signaling pathways related protein p-ERK/t-ERK, p-STAT3/STAT3 and TGF-β were significantly downregulated by FGF21 treatment in a dose dependent manner. The expression of SOCS3 and Nrf-2 were enhanced by treatment with FGF21. The underlying mechanism may be that FGF21 regulates leptin-STAT3 axis via Nrf-2 and SOCS3 pathway in activated HSCs.

scholarly journals Anticonvulsant effect of lercanidipine against pentylenetetrazole induced kindling in mice

2017 ◽  
Vol 6 (9) ◽  
pp. 2134
Author(s):  
Nitya Selvaraj ◽  
Deepa Kameswari ◽  
Ramya Gandhi ◽  
Meher Ali Raja Mohamad
Keyword(s):  
Calcium Channel ◽  
High Voltage ◽  
Scoring System ◽  
Channel Blocker ◽  
Anticonvulsant Effect ◽  
Dependent Manner ◽  
Mice Model ◽  
Dihydropyridine Calcium Channel Blocker ◽  
Dose Dependent

Background: Emerging evidence has demonstrated the role of high-voltage -sensitive activated dihydropyridine (L-type, CaV1.x) channels in the development of epilepsy. Based on that we hypothesized that lercanidipine, a dihydropyridine calcium channel blocker, would protect against Pentylenetetrazole (PTZ) induced kindling in mice model of epilepsy.Methods: Kindling was induced in Swiss albino mice with PTZ in subconvulsive dose (30 mg/kg i.p.) thrice a week for nine weeks and the effect was scored using ‘4 point scoring system’. Rechallenging on the 3rd and 10th day with the same dose of PTZ was carried out after the last chronic dose.Results: The data of the present study demonstrated that pretreatment with lercanidipine (½ h before PTZ, in doses of 1 and 3 mg/kg i.p. daily) alone and in combination with diazepam (2mg/kg i.p.) had decreased the incidence and severity of seizure as well as prolonged the onset of kindling in a dose-dependent manner (p <0.05). On rechallenging, lercanidipine resulted in reduction of seizure score (p <0.05) and increased the seizure latency.Conclusions: The present study suggested that lercanidipine offered neuroprotection against PTZ induced kindling in mice.

scholarly journals Antidiabetes and Anti-Obesity Activity ofLagerstroemia speciosa

2007 ◽  
Vol 4 (4) ◽  
pp. 401-407 ◽  
Author(s):  
Guy Klein ◽  
Jaekyung Kim ◽  
Klaus Himmeldirk ◽  
Yanyan Cao ◽  
Xiaozhuo Chen
Keyword(s):  
Glucose Uptake ◽  
Glucose Transport ◽  
Cell Model ◽  
Water Soluble ◽  
Published Data ◽  
Functional Screening ◽  
Corosolic Acid ◽  
Uptake Assay ◽  
A Cell ◽  
Glucose Uptake Assay

The leaves ofLagerstroemia speciosa(Lythraceae), a Southeast Asian tree more commonly known as banaba, have been traditionally consumed in various forms by Philippinos for treatment of diabetes and kidney related diseases. In the 1990s, the popularity of this herbal medicine began to attract the attention of scientists worldwide. Since then, researchers have conducted numerousin vitroandin vivostudies that consistently confirmed the antidiabetic activity of banaba. Scientists have identified different components of banaba to be responsible for its activity. Using tumor cells as a cell model, corosolic acid was isolated from the methanol extract of banaba and shown to be an active compound. More recently, a different cell model and the focus on the water soluble fraction of the extract led to the discovery of other compounds. The ellagitannin Lagerstroemin was identified as an effective component of the banaba extract responsible for the activity. In a different approach, using 3T3-L1 adipocytes as a cell model and a glucose uptake assay as the functional screening method, Chenet al. showed that the banaba water extract exhibited an insulin-like glucose transport inducing activity. Coupling HPLC fractionation with a glucose uptake assay, gallotannins were identified in the banaba extract as components responsible for the activity, not corosolic acid. Penta-O-galloyl-glucopyranose (PGG) was identified as the most potent gallotannin. A comparison of published data with results obtained for PGG indicates that PGG has a significantly higher glucose transport stimulatory activity than Lagerstroemin. Chenet al. have also shown that PGG exhibits anti-adipogenic properties in addition to stimulating the glucose uptake in adipocytes. The combination of glucose uptake and anti-adipogenesis activity is not found in the current insulin mimetic drugs and may indicate a great therapeutic potential of PGG.

scholarly journals Differential pathways (phospholipase C and phospholipase D) of bradykinin-induced biphasic 1,2-diacylglycerol formation in non-transformed and K-ras-transformed NIH-3T3 fibroblasts. Involvement of intracellular Ca2+ oscillations in phosphatidylcholine breakdown

1992 ◽  
Vol 283 (2) ◽  
pp. 347-354 ◽  
Author(s):  
T Fu ◽  
Y Okano ◽  
Y Nozawa
Keyword(s):  
Phospholipase C ◽  
Phospholipase D ◽  
Dependent Manner ◽  
3T3 Cells ◽  
3T3 Fibroblasts ◽  
Similar Dose ◽  
A Cell ◽  
Nih 3T3 ◽  
Dose Dependent ◽  
Nih 3T3 Cells

Bradykinin (BK) induced a biphasic increase in 1,2-diacylglycerol (DAG) in both K-ras-transformed fibroblasts (DT) and the parent NIH-3T3 cells. The first phase was coincident with the increase in Ins(1,4,5)P3 resulting from PtdIns(4,5)P2 hydrolysis, and the second, sustained, phase was derived from phosphatidylcholine (PtdCho) hydrolysis. In NIH-3T3 cells, stimulation by BK induced greater production of choline than phosphocholine in [3H]choline-labelled cells and appreciable phosphatidylethanol (PtdEtOH) formation in [3H]myristic acid-labelled cells, suggesting that PtdCho was hydrolysed mainly by a phospholipase D (PLD) activity. Pretreatment with propranolol, an inhibitor of phosphatidate phosphohydrolase, markedly diminished the second DAG accumulation, supporting the above notion. In DT cells, BK induced predominantly phosphocholine generation and little PtdEtOH formation, indicating that the PtdCho hydrolysis was due to a phospholipase C (PLC) activity. The BK-induced oscillations in intracellular Ca2+ concentration ([Ca2+]i) observed in single DT cells [Fu, Sugimoto, Oki, Murakami, Okano & Nozawa (1991) FEBS Lett. 281, 263-266] were detected as a sustained [Ca2+]i elevation when assayed in a cell suspension. A receptor-operated Ca2+ channel blocker, SK&F 96365, suppressed both the BK-induced phosphocholine generation and the sustained [Ca2+]i elevation in a similar dose-dependent manner. These results thus suggested that oscillations in [Ca2+]i are involved in the activation of PtdCho-specific PLC in DT cells.

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