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Objective To investigate maternal zinc metabolism and the changes of zinc-related factors as metallothionein-1 (MT1) and zinc transporter-1 (ZnT1) in certain types of congenital heart diseases (CHD).Methods Fifteen infants with interventricular septal defect,12 infants with atrial septal defect and 7 infants with tetralogy of Fallot,together with their mothers were enrolled,and normal infants and their mothers were enrolled by a ratio of 1 ∶ 1 with the above three types of CHD diseases.General conditions of the mothers,along with their diets and zinc-containing drug supplementation during the pregnancy,were surveyed.Maternal blood zinc levels and serum alkaline phosphatase activities at gestation week 32 and delivery or induced abortion,and the protein and mRNA expressions of MT1 and ZnT1 in maternal serum and placental tissue at delivery or induced abortion were assayed.Results The general conditions were comparable between the CHD group and control group.The ratio of the mothers taking more zinc-rich food was significantly lower in the CHD group than in the control group.Circulating zinc levels in interventricular septal defect (73.55±5.79 μmol/L),atrial septal defect (72.66±5.82 μmol/L) and tetralogy of Fallot (68.72±6.72 μmol/L) groups were significantly lower than those in the control groups (82.77± 7.88,84.58 ± 7.55 and 85.66 ± 7.30 μmol/L) at delivery (P all ＜ 0.05).Similar change patterns were seen for serum alkaline phosphatase activities.The relative quantities of serum MT1 and ZnT1 proteins in interventricular septal defect (73.22±36.54 and 68.55± 27.82),atrial septal defect (64.29± 38.26 and 74.55 ± 29.67) and tetralogy of Fallot (67.88± 30.50 and 70.13±29.65) groups were significantly lower than those in their corresponding control groups (166.31±67.43and 97.67±30.22,182.56±71.40 and 111.65±32.70,and 173.81±62.36 and 108.27±28.52,P＜0.01 or P＜0.05).The relative quantities of placental MT1 and ZnT1 proteins and mRNA expressions in interventricular septal defect (protein quantities 0.438±0.096 and 0.384±0.061,mRNA expressions 1.23±0.82 and 0.96±0.39),atrial septal defect (0.427±0.093 and 0.377±0.059,1.17±0.70 and 0.85±0.40) and tetralogy of Fallot (0.414±0.111 and 0.336±0.066,1.31±0.97 and 0.90±0.38) groups were significantly lower than those in their corresponding control groups (protein quantities 0.565±0.083 and 0.541±0.090,mRNA expressions 2.78± 1.06 and 1.67±0.33;protein quantities 0.622±0.136 and 0.493±0.079,mRNA expressions 2.85±0.89 and 1.72±0.38;protein quantities 0.637±0.125 and 0.521±0.089,mRNA expressions 3.21 ± 0.99 and 1.61±0.29;P＜0.01 or P＜0.05).Conclusion Mothers with their fetus of certain types of CHD are found zinc deficiency,and down-regulation of MT1 and ZnT1 expressions in the serum and placenta may involve in the pathogenesis of CHD when maternal zinc deficiency.
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Zinc levels are high in pancreatic β-cells, and zinc is involved in the synthesis, processing and secretion of insulin in these cells. However, precisely how cellular zinc homeostasis is regulated in pancreatic β-cells is poorly understood. By screening the expression of 14 Slc39a metal importer family member genes, we found that the zinc transporter Slc39a5 is significantly down-regulated in pancreatic β-cells in diabetic db/db mice, obese ob/ob mice and high-fat diet-fed mice. Moreover, β-cell-specific Slc39a5 knockout mice have impaired insulin secretion. In addition, Slc39a5-deficient pancreatic islets have reduced glucose tolerance accompanied by reduced expression of Pgc-1α and its downstream target gene Glut2. The down-regulation of Glut2 in Slc39a5-deficient islets was rescued using agonists of Sirt1, Pgc-1α and Ppar-γ. At the mechanistic level, we found that Slc39a5-mediated zinc influx induces Glut2 expression via Sirt1-mediated Pgc-1α activation. These findings suggest that Slc39a5 may serve as a possible therapeutic target for diabetes-related conditions.
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Aims: This study was designed to investigate a common polymorphism in the exon 5 of the solute carrier SLC30A4 (ZNT4) gene 915 T-C in a group of mothers with neural tube defects (NTDs) babies compared to healthy controls in Setif region of Algeria, as well as the detection of a pathogenic mutation of the SLC39A14 (ZIP 14) gene in the NTD group. Methodology: The case-control study, included 94 healthy mothers and 88 mothers with previous NTDs child; aged between 24 and 48 years. Peripheric blood DNA extraction was done by phenol-chloroform method. T915C polymorphism in ZnT4 gene was analyzed by polymerase chain reaction. Furthermore, sequencing of promoter 1: 333 base pairs of ZIP 14 gene was investigated. Odds ratio and Confidence Interval were calculated. Results: Our results revealed that homozygous mutant (CC) carriers in the control group were 6%, and in the NTDs mothers it was 7%, with a risk of 0.97 (CI 95%: (0.29- 3.26). The difference between the allelic frequency of the allele C among NTD s mothers compared to control mothers was not significant (Odds ratio 0.9, CI: 0.57 - 1.43). Sequencing of ZIP 14 gene didn’t show any mutation and alteration in mothers with a previous NTD child. Conclusion: The majority of pregnancies carrying neural tube abnormalities occur in Algerian mothers without previous NTDs cases. Furthermore, despite the lack of a relationship between zinc transporter genes and NTDs in our study, further investigations focusing on the molecular mechanisms and relevance of nutritional zinc status in relation with these malformations should be considered, attempting to find some highlights about pathogenesis of these defects in our country.
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@#[Abstract] Objective: To detect the expression of zinc transporter 1 (ZnT1) gene in glioma tissue, and to explore its effect on the proliferation, migration and invasion of U87 cells. Methods: From October 2015 to January 2017, 20 patients with glioma, who received no chemoradiotherapy before operation, were collected from Department of Neurosurgery, the First Affiliated Hospital of China Medical University. The protein and mRNA content of ZnT1 in glioma tissues and adjacent tissues were detected by Western blotting and Realtime PCR, respectively. ZnT1 and si-ZnT1 plasmids were transfected into glioma U87 cell line respectively to construct ZnT1 over-expression U87 cell line and ZnT1 knockdown U87 cell line. The effects of ZnT1 on proliferation, migration and invasion of U87 cells were detected by MTT and transwell assay. Results: Both mRNA and protein expressions of ZnT1 in glioma tissues was significantly higher than those in adjacent tissues (all P<0.05). U87 cell lines with ZnT1 over-expression and knockdown were successfully constructed. Compared with the control group and empty plasmid control group, the proliferation (0.54±0.01 vs 0.45±0.04, 0.43±0.03, P<0.01), invasion and migration (all P<0.05) of U87 cells with ZnT1 over-expression were significantly increased at 12 h after transfection; however, the proliferation (0.37±0.03 vs 0.45±0.01, 0.44±0.03, P<0.01), invasion and migration (all P<0.05) of U87 cells with ZnT1 knockdown were decreased significantly. Conclusion: ZnT1 was highly expressed in glioma tissues, and promoted the proliferation, migration and invasion of glioma U87 cells.
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As an essential trace element for human,Zn is involved in the synthesis of various enzymes,and plays important roles in the growth and proliferation of cells.At the cellular level,Zn2+ homeostasis is maintained through the complex mechanisms of uptake,storage and excretion,where the Zn transporter families play certain roles.Two major Zn transporter families,namely the SLC30 (ZnT) family and the SLC39 (ZIP) family,have been identified,which act to control the intra-and extracellular equilibrium of Zn2+.While the ZnT family mainly transports Zn out of the cells,while the ZIP family mainly contributes to the uptake and transport of Zn into the cells.The ZIP family has been noted to be associated with various diseases,and be closely related to the development and progression of tumors.Recent studies have suggested low ZIP1 and ZIP2 expression in prostate cancer,high ZIP6,ZIP7 and ZIP10 expression in breast cancer,high ZIP3 and ZIP4 expression in pancreatic cancer,and high ZIP5 and ZIP6 expression in esophageal cancer.The ZIP family may,therefore,function as tumor suppressor genes in prostate cancer,and oncogenes in pancreatic cancer,breast cancer and esophageal cancer.This paper reviews the latest research progress on SLC39 transporter family and tumors.
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Objective To analysis the positive rates of glutamic acid decarboxylase autoantibody (GADA)and zinc transporter 8 autoantibody (ZnT8A)in newly diagnosed type 2 diabetes patients.Methods GADA and ZnT8A were detected in 101 ca-ses of newly diagnosed type 2 diabetes mellitus patients using ELISA.Results The positive rate of GADA was 21.78%,the positive rate of ZnT8A was 17.82%,and the common positive rate of GADA and ZnT8A was 8.91%.There were no corre-lations between GADA or ZnT8A autoantibodies and the patient’s sex (t=-0.724,-0.550;0.903,1.359,P >0.05),age (t=-0.724,-0.550;0.903,1.359,P >0.05),blood glucose (r=0.290,0.110;-0.264,-0.047,P >0.05),cholesterol (r=-0.047,0.004;0.154,-0.138,P >0.05),triglyceride (r=-0.092,-0.054;-0.217,-0.023,P >0.05),and low density lipoprotein (r= - 0.045,- 0.027;0.202,- 0.025,P > 0.05).Conclusion It should be screened autoantibodies timely for newly diagnosed type 2 diabetic patients in order to diagnosis the Latent autoimmune diabetes in adults early.
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Autoimmunity is the main mechanism of type 1 diabetes.The discovery of autoantigens has broadened our understanding of pathogenesis and clinical diagnosis of type 1 diabetes.Insulin,glutamic acid decarboxylase 65,and insulinoma-associated protein 2 have been found to be major autoantigens of type 1 diabetes.In recent years,some autoantigens in type 1 diabetes,such as chromogranin A,islet amyloid polypeptide,zinc transporter 8,and pancreatic duodenal homeobox factor-1,have received some attention in the literature.The purpose of this article is to review the progress of novel autoantigens in type 1 diabetes.
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BACKGROUND: Autophagy is a homeostatic process for intracellular recycling of bulk proteins and aging organelles. Increased autophagy has now been reported in experimental models of traumatic brain injury, stroke and excitotoxicity, and in patients with Alzheimer's disease and critical illness. The role of autophagy in developmental epilepsy, however, is unknown. The present study was to investigate the effects of recurrent neonatal seizure, in the presence and absence of autophagy inhibitor 3-methyladenine (3-MA), on the acute phase gene expression of ZnTs, LC3 and Beclin-1 in rat cerebral cortex and the interaction among them. METHODS: Thirty-six Sprague-Dawley neonatal rats at postnatal day 6(P6) were randomly divided into three groups: a recurrent-seizures group (RS, n=12), a 3-MA treated-seizure group (3-MA group, each rat pretreated with 3-methyladenine before seizures, 100nmol/ l/day, i.p., n=12) and a control group (n=12). At 1.5 and 6 hours after the last seizures, the mRNA levels of ZnT1-ZnT3, microtubule-associated protein 1A/1B light chain 3 (LC3) and beclin-1 were detected using the real-time RT-PCR method. The LC3 protein level was examined by Western blotting. RESULTS: The levels of LC3, beclin-1 and ZnT-2 transcripts in the RS group elevated significantly at 1.5 and 6 hours after the last seizures compared with those in the control and 3-MA groups. At the interval of 1.5 hours, the mRNA level of ZnT-1 increased significantly after the last seizure compared with that in the control group. There was no significant difference in the transcript levels of ZnT-3 among the three groups. Linear correlation analysis showed that the expression of the five genes in the control group exhibited a significant inter-relationship. In the 3-MA group, however, the inter-relationship was only found between beclin-1 and ZnT-1. In the RS group, the inter-relationship was not observed. CONCLUSIONS: The autophagy/lysosomal pathway is immediately activated along with the elevated expression of ZnT1 and ZnT2 in the cerebral cortex after recurrent seizures. 3-MA is involved in the regulation of the autophagy/lysosomal pathway and ZnTs by down-regulating the expression of LC3 and beclin-1.
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Objective To study the effects of zinc on the expression of zinc transporter-7( ZnT-7) in the proliferation of the rat growth plate chondrocytes. Methods Growth plate chondrocytes were isolated from rih cartilage of Wistar rat. The cell3 were treated with zinc chelating agent N, N, N', N'-tetrakis (2-pyridylmethyl )ethylene-diamine (TPEN) of different concentration (0,5,10 and 20 μmol/L) for 12 horns. The expression of rat growth plate chondrocytes specificity collagen type Ⅱ was detected by immunohisloehemistiy. The localization of ZnT-7 was checked by immunofluorescent staining. Real-time RT-PCR and Western blot were used to measure the expression level of ZNT-7 in the cell. Results The result of the immunofluorescence showed that ZnT-7 located in the Golgi apparatus. The expression level of ZnT-7 was slightly higher in the cells treated with 5 μ-mol/L TPEN than the control group, while it was lower in the cells treated with 10 or 20 μmol/L TPEN than the control group. Conclusion ZnT-7 locates in Golgi apparatus and maintains the zinc ion stabilization in the condition of the zinc depletion.
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Objective To explore the effects of physical exercises on recurrent seizures-induced long-term learning and memory deficits and on the expression of zinc transporter-3(ZnT-3)in hippocampuses of developmental period rats.Methods Sprague-Dawley rats aged 21 d were randomly divided into blank control group,exercises control group,seizure group and seizure plus exercises group.Abdominal cavity injections of penicillin or saline were used to induce recurrent seizure or as a control in the corresponding groups.During the postnatal(P)39-44 d and P61-65 d periods,Morris water-maze tests were administered to evaluate spatial learning and memory capacity.During the P48-53 d period,the rats in exercises control and seizure plus exercises groups were subjected to a 30-min daily aerobic exercises program for 6 d.The real-time reverse transcription-polymerase chain reaction(RT-PCR)method was used to detect the expression of ZuT-3 mRNA in hippocampuses of all rats at P66 d. Results Searching strategy:There was a decreasing incidence of marginal strategy and an increasing trend in the use of taxis and straight line strategy in all four groups.The scores on d 1 and 4 were significantly higher in two control groups than in two seizure groups in water-maze test(all P＜0.05).By d 2 the exercises control and seizure plus exercises groups were scoring significantly higher than the bland control and seizure groups(P＜0.05).Memory test:The frequency of passing through the platform quadrant decreased significantly in the two seizure groups compared to the two control groups in both probe tests(all P＜0.05).RT-PCR test:ZnT-3 mRNA expressions in hippocampuses were significantly higher in seizure plus exercises group than in any other groups. Conclusions Penicillin-induced recurrent seizures can induce long-term damage on learning and memory capacity in developmerital period rats.Physical exercises can improve learning capacity.It's mechanism may be related to the up-regulation of ZnT-3 expression in hippocampus of rats.
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Objective To analyze the expression of prolactin protein and ZnT1 mRNA in rat brain in the wake of heat stress and febrile convulsion(FC).Method Thirty-six weanling Spragne-Dawley rats were randomly divided into control group(n=8) and other 28 rats were used to induce heat stroke by warm water but three of them failed to produc expected heat stress.Consequently,there were 35 rats eligible to be models of heat stroke,and of them,10 rats showed heat stress(HS group,n=10) and 15 rats had 5-grade febrile convulsion (FC group,n = 15).The inmmunohistocbemistry and in situ hybridization method were used in this study.The IR) neurons were found in the rats of control group.The deep immune staining was found in the PIR,Era and RS regions of cerebral cortex and light immune staining was found in the PRH,PAR and FR regions of cerebral cortex in HS group.In addition,the PRL-IR positive neurons were found around the midline strip of thalamus without characteristic subnucleus-specific distribution.However,abundant induction of PRL-IR positive neurons with diffuse distribution were found in cerebral cortex,hippoeampus,amygdala,thalamus and hypotha]amns of rats in FC and FC rats showed more PRD-IR positive neurons in cerebral cortex than those in rats of control group (P<ZnT3 mRNA positive cells were seen in I-IS and control group.In contrast,abundant induction of ZnT3 mRNA There is an elevated zinc metabolism in hippocampus of FC group.
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Objective:To observe the growth and development of the weaned mice fed with different levels of dietary zinc and to explore the expression of zinc transporter 3(ZnT3) mRNA induced by different dietary zinc intakes. Methods: Twenty male weaned mice (postnatal day 21) were divided into 4 groups: zinc deficient (ZD), zinc adequate(ZA), zinc supplemental (ZS) and pair fed(PF). Mice were fed with different levels of dietary zinc for 3 weeks (from postnatal day 21 to postnatal day 42) ;the zinc contents of ZD, ZA, ZS and PF group were 1 mg/kg, 30 mg/kg, 180 mg/kg and 180 mg/kg respectively. From postnatal day 21 to postnatal day 42, the diet intakes and weight of the mice were measured everyday. On postnatal day 42, the mice were sacrificed and tissues were immediately isolated and frozen lor RNA extraction. The serum zinc concentrations were measured by AAS and the expression of ZnT3 mRNA was determined by semiquantitative RT-PCR. Results: The dietary intakes and weight of ZD mice were much lower than that of other groups(P3
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AIM:To explore the interaction and function between ZnT3 mRNA expression and zinc elemental distribution in brain slice of mouse.METHODS:Zinc distribution was determined by SRXRF and ZnT3 mRNA expression in tissue was examined by RT-PCR method.RESULTS:Zinc content in cerebral cortex and hippocampus was significantly higher than that in other positions.The highest expression of ZnT3 mRNA was observed in cerebrum,hippocampus and testis.However,the ZnT3 mRNA was not detected in heart,liver,lung,spleen,kidney,intestine,olfactory bulb and cerebellum.CONCLUSION:ZnT3 facilitates the accumulation of zinc in synaptic vesicles and may play important roles in structuring of vesicular zinc pool.
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Objective:To study the concentration response and time course of zinc transporter 1 (ZnT 1) and metallothionein (MT1/MT2) mRNA,as well as the cell viability to zinc exposure in primary cultured new born rats hippocampal neuron s. Methods: The cell viability were determined by trypan blue s taining at various concentrations of Zn 2+ (0, 50, 100, 125, 150, 175, 200 ?mol/L). The expression of ZnT 1, MT1 and MT2 mRNA to various concentrations of zinc exposure(0, 50, 75, 100, 125, 150 ?mol/L) and to 100 ?mol/L zinc exposure for different times (0, 2, 4, 6, 8 h) were determined b y real time fluorescent quantitative PCR. Results: The viabilit y of the neurons decreased significantly after 48 h once the concentration of Zn 2+ exceeded 125 ?mol/L,and the expression of ZnT 1 mRNA was in proportion to the increment of zinc.The expression of MT1/MT2 mRNA reached a plateau when the zinc concentration exceeding 75 ?mol/L. The expression of ZnT 1 mRNA peaked on about 2 h.However, the expression of MT1/MT2 mRNA reached its maximal around 6 h at the concentration of 100 ?mol/L. Conclusion: These results imply that although both MTs and ZnT 1 can attenuate the zinc toxicity, they may play different roles at different phases. ZnT 1 enhance the efflux of zinc prior to the sequesteration by MTs. Th e action of ZnT 1 may be durable, but the role of MTs may be satiable.