Subject(s)
Chilblains/drug therapy , Erythema/chemically induced , Hydroxychloroquine/adverse effects , Lupus Erythematosus, Cutaneous/drug therapy , Pulmonary Eosinophilia/chemically induced , Administration, Cutaneous , Administration, Oral , Aged , Betamethasone/administration & dosage , Drug Therapy, Combination/adverse effects , Drug Therapy, Combination/methods , Eosinophils , Erythema/blood , Erythema/diagnosis , Erythema/drug therapy , Female , Humans , Hydroxychloroquine/administration & dosage , Leukocyte Count , Lung/diagnostic imaging , Prednisolone/therapeutic use , Pulmonary Eosinophilia/blood , Pulmonary Eosinophilia/diagnosis , Pulmonary Eosinophilia/drug therapy , Skin/drug effects , Skin/pathology , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
Medication therapy is the first line of treatment in the management of epilepsy. Fetal exposure to valproic acid (VPA), an antiepileptic drug, poses an elevated risk of teratogenicity in early pregnancy. Some studies have reported that monocarboxylate transporters (MCTs) may be involved in the placental transport of VPA. However, it has not been determined which MCTs contribute to VPA transport into the placenta. Therefore, the aim of this study was to determine how MCTs contribute to VPA transport into the placenta using the human placenta choriocarcinoma cell line JEG-3. VPA uptake was investigated using JEG-3 cells and radiolabeled VPA. MCT expression in JEG-3 cells was detected using RT-PCR and western blotting. Knockdown of MCTs was carried out using siRNAs. VPA uptake into JEG-3 cells was pH- and concentration-dependent, and described by using the Michaelis-Menten equation (Km = 0.95 ± 0.17 mM; Vmax = 19.3 ± 1.21 nmol/mg protein/15 s). MCT1 and MCT4 expression was found in JEG-3 cells, and typical MCT inhibitors significantly inhibited VPA uptake into JEG-3 cells. However, knockdown of MCT1 and MCT4 did not alter VPA uptake. In conclusion, VPA transport is mediated by a proton-dependent transporter in JEG-3 cells, but not by MCT1 and MCT4.
Subject(s)
Monocarboxylic Acid Transporters , Muscle Proteins , Protons , Symporters , Valproic Acid/metabolism , Biological Transport , Cell Line, Tumor , Humans , Hydrogen-Ion Concentration , Monocarboxylic Acid Transporters/antagonists & inhibitors , Monocarboxylic Acid Transporters/genetics , Monocarboxylic Acid Transporters/metabolism , Muscle Proteins/antagonists & inhibitors , Muscle Proteins/genetics , Muscle Proteins/metabolism , RNA, Small Interfering/pharmacology , Symporters/antagonists & inhibitors , Symporters/genetics , Symporters/metabolism , Valproic Acid/antagonists & inhibitorsABSTRACT
Glioblastoma (GBM) is the most common brain tumor; however, no effective treatment for it is available yet. Monocarboxylate transporters, which are highly expressed in GBM, play a role in transporting antitumor agents, such as 3-bromopyruvate (3-BrPA). Valproate, primarily used to treat epilepsy, has been considered a possible treatment option for malignant GBM. In this study, we aimed to investigate the combined effects of 3-BrPA and valproate on GBM cell growth and elucidate the underlying mechanisms. Valproate enhanced 3-BrPA-induced cell death in T98G cells, used as a GBM model. Multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP) mRNA levels significantly increased after valproate treatment. 3-BrPA-induced cell death, which was enhanced by valproate, was inhibited in the presence of MK571, a MRP inhibitor, or Ko143, a BCRP inhibitor. In addition, treatment with 3-BrPA and valproate for 48â¯h reduced cellular ATP levels compared to those in the 3-BrPA alone treatment group. However, cellular ATP levels were recovered in the presence of MK571 or Ko143, compared to those in the 3-BrPA and valproate treatment groups. In conclusion, we suggested that valproate enhanced 3-BrPA-induced cell death. This might be attributable to the increase in cellular ATP consumption owing to valproate-induced MRP2 or BCRP expression.
Subject(s)
Antineoplastic Agents/administration & dosage , Brain Neoplasms/drug therapy , Glioblastoma/drug therapy , Pyruvates/administration & dosage , Valproic Acid/administration & dosage , ATP-Binding Cassette Transporters/genetics , Adenosine Triphosphate/metabolism , Brain Neoplasms/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Glioblastoma/metabolism , Humans , RNA, Messenger/metabolismABSTRACT
Understanding the interplay between the topological nature and the symmetry property of interacting systems has been a central matter of condensed matter physics in recent years. In this Letter, we establish nonperturbative constraints on the quantized Hall conductance of many-body systems with arbitrary interactions. Our results allow one to readily determine the many-body Chern number modulo a certain integer without performing any integrations, solely based on the rotation eigenvalues and the average particle density of the many-body ground state.
ABSTRACT
Gabapentin (GBP) is a widely used antiepileptic drug, with potential for use in the treatment of epilepsy in pregnant women. Although studies have examined GBP transport mechanisms across the blood-brain barrier, kidney, and intestine, the mechanism in the placenta has not been fully elucidated. We previously reported that GBP accumulates at high concentrations in human placental choriocarcinoma BeWo cells. The purpose of this study was to examine the transport mechanism of GBP in placental choriocarcinoma cells (BeWo and JEG-3), and to identify the carrier involved. High concentrations of intracellular GBP accumulations were also found in JEG-3 cells. A kinetic analysis showed that a single carrier system was involved in the uptake of GBP. Furthermore, substrates for l-type amino acid transporter (LAT) and siRNAs targeted to LAT1 significantly decreased GBP uptake. Our observations from this study suggest that LAT1 is the main contributor to GBP transport in placental choriocarcinoma cells.
