1.Progress in the study of multidrug and toxin extrusion proteins.
Acta Pharmaceutica Sinica 2014;49(8):1105-1110
Mammal multidrug and toxin extrusion proteins (MATEs) play an important role in the transport of organic cations in the body. MATEs mediate the final excretion step for multiple organic cation drug used clinically and important endogenous substances. This article reviews the discovery, type, gene coding and polymorphism, body distribution, classification of substrates and inhibitors and their research method of MATEs. The article also discusses the major research significance of MATEs with examples.
Animals
;
Biological Transport
;
Cations
;
Organic Cation Transport Proteins
;
metabolism
;
Polymorphism, Genetic
2.A pair of transporters controls mitochondrial Zn2+ levels to maintain mitochondrial homeostasis.
Tengfei MA ; Liyuan ZHAO ; Jie ZHANG ; Ruofeng TANG ; Xin WANG ; Nan LIU ; Qian ZHANG ; Fengyang WANG ; Meijiao LI ; Qian SHAN ; Yang YANG ; Qiuyuan YIN ; Limei YANG ; Qiwen GAN ; Chonglin YANG
Protein & Cell 2022;13(3):180-202
Zn2+ is required for the activity of many mitochondrial proteins, which regulate mitochondrial dynamics, apoptosis and mitophagy. However, it is not understood how the proper mitochondrial Zn2+ level is achieved to maintain mitochondrial homeostasis. Using Caenorhabditis elegans, we reveal here that a pair of mitochondrion-localized transporters controls the mitochondrial level of Zn2+. We demonstrate that SLC-30A9/ZnT9 is a mitochondrial Zn2+ exporter. Loss of SLC-30A9 leads to mitochondrial Zn2+ accumulation, which damages mitochondria, impairs animal development and shortens the life span. We further identify SLC-25A25/SCaMC-2 as an important regulator of mitochondrial Zn2+ import. Loss of SLC-25A25 suppresses the abnormal mitochondrial Zn2+ accumulation and defective mitochondrial structure and functions caused by loss of SLC-30A9. Moreover, we reveal that the endoplasmic reticulum contains the Zn2+ pool from which mitochondrial Zn2+ is imported. These findings establish the molecular basis for controlling the correct mitochondrial Zn2+ levels for normal mitochondrial structure and functions.
Animals
;
Caenorhabditis elegans/metabolism*
;
Cation Transport Proteins/genetics*
;
Homeostasis
;
Mitochondria/metabolism*
;
Zinc/metabolism*
3.Structure and function of heavy metal transporter P(1B)-ATPase in plant: a review.
Yuxiu ZHANG ; Yuanya ZHANG ; Tao SUN ; Tuanyao CHAI
Chinese Journal of Biotechnology 2010;26(6):715-725
The regulation of the heavy-metal accumulation in vivo for plant survival is very complex. The metal cation transporter plays key roles in the metabolic process. P(1B)-ATPases are the only subgroup of P-ATPases that contribute to heavy metal homeostasis presented in most organisms. Arabidopsis thaliana contains eight genes encoding P(1B)-ATPases. The current reports show that the functions of P(1B)-ATPases are involved in maintaining metal homeostasis, transporting and detoxification in plants. P(1B)-ATPases not only mediated metal ion mobilization and uptake in roots, but also contribute to the metal transport, storage and tolerance in shoots, especially in heavy metal hyperaccumulators. In this paper, we reviewed and discussed the evolution, classification, structure and function of P(1B)-ATPases in plants. HMAs-transgenic manipulation could be a feasible approach for phytoremediation and mineral nutrition fortification.
Adenosine Triphosphatases
;
genetics
;
metabolism
;
Biodegradation, Environmental
;
Biological Transport
;
physiology
;
Cation Transport Proteins
;
classification
;
genetics
;
metabolism
;
Metals, Heavy
;
metabolism
;
Plant Proteins
;
genetics
;
metabolism
;
Plants
;
enzymology
;
genetics
;
metabolism
4.Increased DMT1 expression and iron content in MPTP-treated C57BL/6 mice.
Hong JIANG ; Zhong-Ming QIAN ; Jun-Xia XIE
Acta Physiologica Sinica 2003;55(5):571-576
Iron plays a key role in Parkinson s disease (PD). To illustrate the mechanism underlying the increase of iron in substantia nigra (SN) in PD, changes of the expression of divalent metal transporter 1 (DMT1) and iron content were examined in SN in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated mice using immunohistochemistry and histochemistry respectively. Following MPTP treatment for 3 d, elevated iron staining was found in SN. A further increase in iron content was observed after 7 d. In these lesioned animals, tyrosine hydroxylase-immunoreactive DA neurons exhibited a decrease in number and morphological changes as well. There were two isoforms of DMT1 expressed in SN of mice. After MPTP treatment, the expression of DMT1 without IRE form increased in either group, whereas DMT1 with IRE form increased only after 7 d of MPTP treatment. These observations suggest that DMT1 is possibly involved in the process of iron accumulation in SN of MPTP-treated mice, which might be responsible for the subsequent death of DA neurons.
Animals
;
Cation Transport Proteins
;
metabolism
;
Dopamine
;
metabolism
;
Iron
;
metabolism
;
Iron-Binding Proteins
;
metabolism
;
Mice
;
Mice, Inbred C57BL
;
Parkinsonian Disorders
;
metabolism
;
Protein Isoforms
;
metabolism
;
Substantia Nigra
;
metabolism
;
Transferrin
;
metabolism
5.Current and Future Clinical Applications of Zinc Transporter-8 in Type 1 Diabetes Mellitus.
Bo YI ; Gan HUANG ; Zhi-Guang ZHOU
Chinese Medical Journal 2015;128(17):2387-2394
OBJECTIVETo evaluate the utility of zinc transporter-8 (ZnT8) in the improvement of type 1 diabetes mellitus (T1DM) diagnosis and prediction, and to explore whether ZnT8 is a potential therapeutic target in T1DM.
DATA SOURCESA search was conducted within the medical database PubMed for relevant articles published from 2001 to 2015. The search terms are as follows: "ZnT8," "type 1 diabetes," "latent autoimmune diabetes in adults," "type 2 diabetes," "islet autoantibodies," "zinc supplement," "T cells," "β cell," "immune therapy." We also searched the reference lists of selected articles.
STUDY SELECTIONEnglish-language original articles and critical reviews concerning ZnT8 and the clinical applications of islet autoantibodies in diabetes were reviewed.
RESULTSThe basic function of ZnT8 is maintaining intracellular zinc homeostasis, which modulates the process of insulin biosynthesis, storage, and secretion. Autoantibodies against ZnT8 (ZnT8A) and ZnT8-specific T cells are the reliable biomarkers for the identification, stratification, and characterization of T1DM. Additionally, the results from the animal models and clinical trials have shown that ZnT8 is a diabetogenic antigen, suggesting the possibility of ZnT8-specific immunotherapy as an alternative for T1DM therapy.
CONCLUSIONSZnT8 is a novel islet autoantigen with a widely potential for clinical applications in T1DM. However, before the large-scale clinical applications, there are still many problems to be solved.
Animals ; Autoantibodies ; immunology ; Autoantigens ; immunology ; Cation Transport Proteins ; immunology ; metabolism ; Diabetes Mellitus, Type 1 ; immunology ; metabolism ; Humans
6.Expressions of SLC22A14 and SPAG6 proteins in the ejaculated sperm of idiopathic asthenozoospermia patients.
Fang-Yuan HUO ; Yu-Shan LI ; Xi-Yang YANG ; Quan-Xian WANG ; Jun-Jie LIU ; Lin-Kai WANG ; Yan-Hua SU ; Lin SUN
National Journal of Andrology 2017;23(8):703-707
Objective:
To investigate the expressions of solute carrier family 22 member 14 (SLC22A14) and sperm-associated antigen 6 (SPAG6) in the sperm of idiopathic asthenospermia men.
METHODS:
We collected semen samples from 50 idiopathic asthenozoospermia patients and another 50 normal sperm donors, purified the sperm by discontinuous density centrifugation on Percoll gradients, and then determined the mRNA and protein expressions of SLC22A14 and SPAG6 by RT-PCR and Western blot, respectively.
RESULTS:
Compared with the normal controls, the idiopathic asthenozoospermia patients showed significantly decreased mRNA expressions of SLC22A14 (0.77 ± 0.08 vs 0.53 ± 0.10, P<0.01) and SPAG6 (0.78 ± 0.09 vs0.52 ± 0.10 , P<0.01) and protein expressions of SLC22A14 (0.80 ± 0.09 vs 0.55 ± 0.10 , P<0.01) and SPAG6 (0.78 ± 0.09 vs 0.56 ± 0.09, P<0.01).
CONCLUSIONS
T The expressions of SLC22A14 and SPAG6 are reduced in the sperm of the patients with idiopathic asthenospermia, which may be one of the important causes of asthenospermia.
Asthenozoospermia
;
metabolism
;
Blotting, Western
;
Ejaculation
;
Humans
;
Male
;
Microtubule Proteins
;
genetics
;
metabolism
;
Organic Cation Transport Proteins
;
genetics
;
metabolism
;
Proteomics
;
RNA, Messenger
;
metabolism
;
Sperm Motility
;
Spermatozoa
;
metabolism
7.Experimental Penicillin-Induced Seizure.
Journal of Korean Neurosurgical Society 1981;10(2):427-434
The penicillin produces seizures when applied directly to cerebral cortex and, in some instances, when given systemically in large amounts. Most studies with this agent have had as their goal the elucidation of neurophysiological mechanisms underlying seizure activity. The present study was undertaken to explore the biochemical events which take place in the presence of an epileptogenic agent and, in particular, to see whether this agent has a direct effect on passive or active cation transport or an effect on energy production within neural tissues. The penicillin-induced seizure activity has been produced by direct injection of an aqueous penicillin G sodium into the cerebral subarachnoid space in rat. It is assumed that penicillin-induced seizure results from the leakage of potassium ions from intracellular compartment and alteration of firing properties of neurons with prolonged depolarization, and disturbances in activities of enzyme involved in glutamine metabolism. Diphenylhydantoin may stimulate cation pumping with activation of (Na+-K+)-ATPase enzyme system and this action may be relevant to its anticonvulsant activity.
Animals
;
Cation Transport Proteins
;
Cerebral Cortex
;
Fires
;
Glutamine
;
Ions
;
Metabolism
;
Neurons
;
Penicillin G
;
Penicillins
;
Phenytoin
;
Potassium
;
Rats
;
Seizures*
;
Subarachnoid Space
8.Establishment of MDCK cell models expressing human MATE1 or co-expressing with human OCT1 or OCT2.
Hong-mei LEI ; Si-yuan SUN ; Li-ping LI ; Mei-juan TU ; Hui ZHOU ; Su ZENG ; Hui-di JIANG
Acta Pharmaceutica Sinica 2015;50(7):842-847
To establish single- and double-transfected transgenic cells stably expressing hMATE1, hMATE1 cDNA was cloned by RT-PCR from human cryopreserved kidney tissue, and subcloned into pcDNA3.1(+) plasmid by virtue of both HindIII and Kpn I restriction enzyme sites. Subsequently, the recombined pcDNA3.1(+)- hMATE1 plasmid was transfected into MDCK, MDCK-hOCT1 or MDCK-hOCT2 cells using Lipofectamine 2000 Reagent. After a 14-day-cultivation with hygromycin B at the concentration of 400 µg · mL(-1), all clones were screened with DAPI and MPP+ as substrates to identify the best candidate. The mRNA content of hMATE1, the cellular accumulation of metformin with or without cimetidine as inhibitor, or transportation of cimetidine was further valuated. The results showed that all of the three cell models over expressed hMATE1 mRNA. The cellular accumulation of metformin in MDCK-hMATE1 was 17.6 folds of the control cell, which was significantly inhibited by 100 µmol · L(-1) cimetidine. The transcellular transport parameter net efflux ratios of cimetidine across MDCK-hOCT1/hMATE1 and MDCK-hOCT2/hMATE1 monolayer were 17.5 and 3.65, respectively. In conclusion, cell models with good hMATE1 function have been established successfully, which can be applied to study the drug transport or drug-drug interaction involving hMATE1 alone or together with hOCT1/2 in vitro.
Animals
;
Biological Transport
;
Cimetidine
;
pharmacology
;
DNA, Complementary
;
Dogs
;
Drug Interactions
;
Humans
;
Madin Darby Canine Kidney Cells
;
Metformin
;
pharmacology
;
Organic Cation Transport Proteins
;
genetics
;
metabolism
;
Transfection
9.Uptake of nickel from industrial wastewater by genetically engineered Escherichia coli JM109.
Xu DENG ; Qing-Biao LI ; Ying-Hua LU ; Dao-Hua SUN ; Yi-Li HUANG
Chinese Journal of Biotechnology 2003;19(3):343-348
Heavy metal wastewater poses a serious threat to the environment. In comparison to the existing methods of chemical precipitation, ion exchange and carbon adsorption, biosorption is an attractive alternative for the recovery of heavy metals from industrial effluents. However, nickel ion, different from other heavy metal ions, is a more recalcitrant pollutant and has low affinity to many metal tolerant microorganisms. In this study, Escherichia coli JM109 was genetically engineered to simultaneously express a Ni2+ transport system (the product of nixA gene) andoverexpress metallothionein (MT). NixA protein has a high affinity for Ni2+, and metallothioneins (MTs) are capable of binding a variety of heavy metals including Ni2+ . The Ni2+ bioaccumulation performance of the genetically engineered E. coli JM109 was evaluated. Time-course test showed that the bioaccumulation rate was rapid, and 95% of the accumulation was achieved within the first 10 minutes. The maximum Ni2+ bioaccumulation by genetically engineered E. coli cells was dramatically increased from 1.54 mg/g to 10.11mg/g, a more than five-fold increase than that of the original E. coli strain. The isotherm was of Langmuir type. Within the tested pH range (pH 4-10), the engineered cells displayed more resistance to pH variation, retaining up to 80% of the Ni2+ binding capacity at pH 4, while the original E. coli host cells lost 80% of Ni2+ binding capacity at pH 4. The presence of Na+ and Ca2+ affected Ni2+ bioaccumulation, but the effects were not serious, as 71% and 66% of the Ni2+ binding capacities were retained respectively at the concentrations of 1000 mg/L Na+ and 1000 mg/L Ca2+ . However, Mg2+ exerted a severe adverse effect on Ni2+ bioaccumulation, 83% of Ni2+ accumulating capacity was lost when Mg2+ concentration reached 200 mg/L. The effects of different kinds of heavy metals on Ni2+ accumulating were different. The genetically engineered E. coli cell lost less than 45% of its Ni2+ bioaccumulation activity in the presence of 50 mg/L lead or cadmium, 66% in the presence of 25mg/L mercury and 84% in the presence of 40 mg/L copper. The presence of glucose did not improve Ni2+ uptake. Our study suggests that the genetically engineered E. coli JM109 has potential application for effective and efficient recovery of nickel from aqueous solutions.
Biodegradation, Environmental
;
Cation Transport Proteins
;
genetics
;
metabolism
;
Escherichia coli
;
genetics
;
metabolism
;
Genetic Engineering
;
methods
;
Hydrogen-Ion Concentration
;
Metallothionein
;
genetics
;
metabolism
;
Nickel
;
metabolism
;
Water Pollutants, Chemical
;
metabolism
10.Functional characterization of a potassium transporter gene NrHAK1 in Nicotiana rustica.
Zhao-kui GUO ; Qian YANG ; Xiu-qing WAN ; Pei-qiang YAN
Journal of Zhejiang University. Science. B 2008;9(12):944-952
The purpose of this study is to investigate the function of a novel potassium transporter gene (NrHAK1) isolated from Nicotiana rustica roots using yeast complement and real-time PCR technique. The complementary DNA (cDNA) of NrHAK1, 2 488 bp long, contains an open reading frame (ORF) of 2 334 bp encoding a protein of 777 amino acids (87.6 kDa) with 12 predicted transmembrane domains. The NrHAK1 protein shows a high sequence similarity to those of high-affinity potassium transporters in Mesembryanthemum, Phytolacca acinosa, Arabidopsis thaliana, and so on. We found that the NrHAK1 gene could complement the yeast-mutant defect in K+ uptake. Among several tissues surveyed, the expression level of NrHAK1 was most abundant in the root tip and was up-regulated when exposed to potassium starvation. Moreover, the transcript accumulation was significantly reduced by adding 5 mmol/L NH4+ to the solution. These results suggest that NrHAK1 plays an important role in potassium absorption in N. rustica.
Cation Transport Proteins
;
chemistry
;
genetics
;
physiology
;
Plant Proteins
;
chemistry
;
genetics
;
physiology
;
Potassium
;
metabolism
;
Quaternary Ammonium Compounds
;
pharmacology
;
Sodium
;
pharmacology
;
Tobacco
;
genetics
;
metabolism