OBJECTIVETo investigate the mRNA expression of monocarboxylate transporter 8 (MCT8), a thyroid hormone transport protein, in the lateral ventricle of rats with cerebral ischemia.

METHODSImmunofluorescence staining was used to observe the expression of MCT8 in the lateral ventricle of 5 normal SD rats. Another 20 adult male SD rats were randomized into 4 groups and subject to permanent ligation of both the common carotid arteries (2-vessel occlusion, 2VO) for 3 days, 2 weeks, or 5 weeks, or no ligation (control). At the end of the experiment, the transcriptional level of MCT8 in the brain tissue of the rats were detected using fluorescent quantitative PCR.

RESULTSMCT8 mRNA levels in 3-day and 2-week 2VO groups were comparable with that in the control group (P=0.909; P=0.694), but increased significantly in 5-week 2VO group compared with that in the control and 3-day 2VO groups (P=0.029; P=0.023). No significance was found in MCT8 mRNA between the 2-week and 5-week 2VO groups (P=0.065).

CONCLUSIONProlonged cerebral ischemia causes compensatory increase of MCT8 mRNA expression on the capillary endothelial cell membranes in the lateral ventricle of rats.

Animals ; Brain ; metabolism ; Brain Ischemia ; metabolism ; Cerebral Infarction ; metabolism ; Male ; Monocarboxylic Acid Transporters ; metabolism ; Rats ; Rats, Sprague-Dawley

BACKGROUNDIodine deficiency is a major factor affecting thyroid auto-regulation, the quantity of iodine may greatly influence the synthesis of thyroid hormones (THs). It has long been believed that TH enters the cell through passive diffusion. Recent studies have suggested that several transporters could facilitate transportation of TH. The monocarboxylate transporter 8 (MCT8) was identified as a very active and specific TH transporter. The purpose of this study was to investigate whether iodine insufficient affected the expression of MCT8 in the thyroid gland.

METHODSSixty BALB/c mice were randomly divided into two groups: control group was fed with standard feed (iodine concentration of 300 µg/kg); while low-iodine (LI) group received iodine-insufficient feed (iodine concentration of 20-40 µg/kg). After 3 months, 10 mice of each group were sacrificed. The remaining 20 mice of each group were kept till 6 months. From the LI group, we randomly selected 15 mice and injected triiodothyronine (T3, 100 µg/kg body weight per day) intraperitoneally for 24, 48 or 72 hours (5 mice for each time-point). Then, all the mice were sacrificed. Mouse serum thyroxine (T4), T3, and thyroid-stimulating hormone (TSH) levels were determined by chemiluminescence immunoassay (CIA). The protein content or messenger RNA (mRNA) level of thyroid MCT8 was measured by Western blotting analysis or real time RT-PCR respectively. MCT8 subcellular location in thyroid tissues was probed with immunohistochemistry (IHC) assay.

RESULTSWe found that mouse serum T3 and T4 levels decreased and TSH level increased by the end of the third month. Consistent with these findings, there was significant goiter and hypothyroidism in the LI group. Meanwhile, the MCT8 mRNA increased to 1.36-fold of the level in the control group at the 3(rd) month. At 6(th) month, the serum T4 level in LI mice remained at a lower level, and MCT8 mRNA expression continued rising to nearly 1.60-fold compared with the control group. The protein content was also about 3 times higher than that in the control group. IHC results also revealed MCT8 was of higher expression and localized in the cytoplasm of thyroid follicular cells. After providing exogenous T3 to iodine deficient mice, the serum T3 and T4 gradually increased, whereas MCT8 mRNA and protein both started to decrease and returned to the same level as the control group.

CONCLUSIONThere is a compensatory increase in thyroid MCT8 expression to enhance its capability to transport TH from thyroid to the blood circulation in iodine deficient mice.

Animals ; Iodine ; deficiency ; Mice ; Mice, Inbred BALB C ; Monocarboxylic Acid Transporters ; genetics ; metabolism ; Thyroid Gland ; metabolism ; Thyrotropin ; blood ; Thyroxine ; blood ; Triiodothyronine ; blood

PURPOSE: The aim of this study was to investigate the differences of expression in glycolysis-related proteins such as Glut-1, carbonic anhydrase (CA) IX, and monocarboxylate transporter (MCT) 4 according to the myoepithelial cell (MEC) and basement membrane (BM) status in solid papillary carcinoma (SPC) of the breast. MATERIALS AND METHODS: Immunohistochemical evaluation of Glut-1, CAIX, and MCT4, as well as p63 and type IV collagen, were performed on 23 SPC cases. RESULTS: Six and nine cases of SPC showed the presence and absence of myoepithelial cells, respectively, and eight cases belonged to the borderline status (p63-positive MEC on some areas of the outer tumor surface but not in others). BM was partially or completely absent in 14 cases and present in nine cases. SPC lacking BM more frequently showed high expression of CAIX than SPC with BM (p=0.037). CONCLUSION: In SPC of the breast, a strong expression of CAIX seems to be associated with an increasing degree of loss of BM, which can be interpreted as BM degradation due to the induction of extracellular acidity with increasing expression of CAIX.
Adult ; Aged ; Basement Membrane/*metabolism ; Breast Neoplasms/*metabolism ; Carcinoma, Papillary/*metabolism ; Excitatory Amino Acid Transporter 2/metabolism ; Female ; Glycolysis ; Humans ; Immunohistochemistry ; Middle Aged ; Monocarboxylic Acid Transporters/metabolism ; Muscle Proteins/metabolism ; Tumor Markers, Biological/*metabolism

OBJECTIVETo investigate the changes in the levels of monocarboxylate transporter-2 in spinal cord horn in a rat model of chronic inflammatory pain.

METHODSMale SD rats weighting 180 - 220 g were randomly divided into two groups(n = 48): normal saline group (NS group), complete Freund's adjuvant group (CFA group). Rats were given injections of CFA 100 µl in left hind paw in group CFA, and an equal volume of saline was given injection in group NS. Mechanical withdraw threshold(MWT) and thermal withdraw latency(TWL) were measured at before injection(T0 and 3 h, 1 d, 3 d, 7 d, 14 d, and 21 d after injection(T1-7). Four rats were chosen from each group at T0-7 and sacrificed, and L4-5 segments of the spinal cord horn were removed for measurement of the expression of monocarboxylate transporter-2 by Western blot analysis.

RESULTSIn CFA group, mechanical hyperalgesia and allodynia appeared on the 3 h after CFA injection, then until the day 14. The expression of monocarboxylate transporter-2 in the spinal dorsal horn of rats in CFA group was significantly higher than that in normal control group at T1-6(P <0.05). The protein level of monocarboxylate transporter-2 was apparently correlated with MWT and TWL(P <0.01 and P <0.05) in CFA group.

CONCLUSIONThe level of monocarboxylate transporter-2 in spinal dorsal horn is significantly increased in a rat model of chronic inflammatory pain and the change may involve in the formation and maintenance of central sensitization in spinal cord of chronic inflammatory uain.

Animals ; Disease Models, Animal ; Freund's Adjuvant ; Hyperalgesia ; chemically induced ; Inflammation ; chemically induced ; metabolism ; Male ; Monocarboxylic Acid Transporters ; metabolism ; Pain ; chemically induced ; metabolism ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; metabolism ; physiopathology

OBJECTIVETo investigate brazilein's role in energy metabolism of cerebral ischemia-reperfusion in mice.

METHODFourty mice were randomly divided into the sham group, ischemia group, brazilein 5 mg x kg(-1) group and brazilein 10 mg x kg(-1) group, each with ten cases. Cerebral ischemia model was the built. Mice were injected with brazilein three days before the operation, then they were killed. Cerebrum homogenate was prepared for the detecting of ATP, ADP, AMP and lactic acid by HPLC, expressions of MCT1 and MCT2 in mRNA level by RT-PCR.

RESULTThe lactic acid in cerebrum increased sharply 20 minutes after cerebral ischemia and decreased 1 hour after reperfusion, then returned to the normal level 24 hours after reperfusion. The charge of energy decreased significantly at the beginning of the ischemia-reperfusion, and the charge restored 1 hour after reperfusion though it was still much lower than the normal level at the time point of 24 hours. Moreover, MCT1 and MCT2 upregulated accompanied with the increase of lactate, MCT2 mRNA enhanced in brazilein 5 mg x kg(-1) group (P < 0.05) while both the two factors increased in brazilein 10 mg x kg(-1) group (P < 0.01).

CONCLUSIONBrazilein might protect neurons by changing the charge of energy.

Animals ; Benzopyrans ; administration & dosage ; Brain Ischemia ; drug therapy ; genetics ; metabolism ; Disease Models, Animal ; Energy Metabolism ; drug effects ; Gene Expression ; drug effects ; Humans ; Indenes ; administration & dosage ; Male ; Mice ; Mice, Inbred ICR ; Monocarboxylic Acid Transporters ; genetics ; metabolism ; Random Allocation ; Reperfusion Injury ; drug therapy ; genetics ; metabolism ; Symporters ; genetics ; metabolism

Poloxamers are found to be an efficient adjuvant with multiple effects and are applied generally in pharmaceutical field. In recent years, it is investigated that poloxamers can increase the permeability of a broad spectrum of drugs through blood-brain barrier (BBB) by means of manifold mechanisms included: (1) inhibiting P-glycoprotein and multidrug-resistance associated protein efflux systems on BBB; (2) adsorbing different apolipoproteins in plasma on the surface of poloxamer-coated nanoparticles, which could interact with BBB through different receptors and mechanisms; (3) connecting to specific ligands and monoclonal antibodies to cross the BBB via specific endogenous transporters localized within the brain capillary endothelium. Significant roles of poloxamer in drug transport across BBB are considered in this review which provides for important guidance to the design of brain-targeted drug delivery system.
ATP Binding Cassette Transporter, Sub-Family B ; antagonists & inhibitors ; metabolism ; ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters ; antagonists & inhibitors ; metabolism ; Animals ; Blood-Brain Barrier ; drug effects ; metabolism ; Brain ; metabolism ; Drug Carriers ; Drug Delivery Systems ; Excipients ; pharmacology ; Glucose Transport Proteins, Facilitative ; antagonists & inhibitors ; metabolism ; Humans ; Monocarboxylic Acid Transporters ; antagonists & inhibitors ; metabolism ; Multidrug Resistance-Associated Proteins ; antagonists & inhibitors ; metabolism ; Nanoparticles ; Permeability ; Poloxamer ; chemistry ; pharmacology