• Korean Journal of Acupuncture
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• v.38 no.3
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• pp.133-139
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• 2021

Objectives : Parkinson's disease is a neurodegenerative disease caused by a decrease in the dopaminergic neurons in the substantia nigra. The abnormal expression of solute carrier family 6 member 4 (Slc6a4) has been reported in patients with Parkinson's disease. Methods : In this study, we used MPTP to examine the changes in the expression of Slc6a4 in the brain of mice with Parkinson's disease and investigate its effect on dopaminergic neuronal cell death. Results : In the examination of the Slc6a4 expression in the substantia nigra of MPTP-treated mice for 4 weeks. The gene expression was increased compared to the normal group. To investigate the relationship between Slc6a4 and dopaminergic neurons, we performed a study using siRNA of Slc6a4 in the dopaminergic neuronal cell line SH-SY5Y. Using the siRNA of Slc6a4 to evaluate gene expression, it revealed that the tyrosine hydroxylase (TH) expression increases when Slc6a4 decreases. Moreover, this confirms its effects on the dopaminergic neurons. Additionally, through the evaluation of factors related to apoptosis, in particular, it was established that the value of bax/bcl2 decreased and was affected. These results suggest that a decreased Slc6a4 expression induces an increase in TH expression, providing a mechanism of action for dopaminergic neurons regulated by Slc6a4 expression. Conclusions : Slc6a4 is deemed to be involved in the regulation of dopaminergic neurons, suggesting that an increased Slc6a4 expression induced by MPTP may influence a reduction of dopaminergic neurons.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.21 no.1
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• pp.23-30
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• 2010

Objectives ： This study aimed to examine the association between norepinephrine transporter gene (SLC6A2) polymorphisms and attention-deficit hyperactivity disorder (ADHD) and to examine the relationship between the genotypes and allele variants of SLC6A2 and results of the Korean version of the parent ADHD rating scale (K-ARS). Methods ： We examined the association between ADHD and norepinephrine transporter gene polymorphism using DNA from 137 Korean children with ADHD and 120 normal controls. We compared the genotype distributions and allele frequencies of SLC6A2 polymorphism between the control group and the ADHD group. Then, we correlated the children's K-ARS mean totals, inattention scores, and hyperactivity/impulsivity scores with the genotypes and alleles for each SLC6A2 polymorphism. Results ： There were no significant differences in genotype and allele distribution for each SLC6A2 polymorphism, as shown by the Chi-square test (p>.01). There was a trend toward a difference in allele frequency in rs 5568, but it was not statistically significant after adjusting for multiple comparisons (p=.048). Also, there were no significant differences in K-ARS scores according to the genotypes and alleles for the SLC6A2 polymorphisms. Conclusion ： Our study found no significant evidence of an association between SLC6A2 polymorphisms and ADHD.

• Korean Journal of Biological Psychiatry
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• v.16 no.2
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• pp.121-126
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• 2009

Objectives : The serotonin transporter gene(SLC6A4) is one of the most widely studied candidate genes in autism spectrum disorder(ASD), but there have been conflicting results from studies into the association between SLC6A4 and ASD. The aim of this study was to evaluate the association between single nucleotide polymorphisms(SNPs) in the SLC6A4 gene and ASD in the Korean population. Methods : We selected 12 SNPs in SLC6A4 and observed the genotype of 151 Korean ASD trios. We tested the family-based association for each individual polymorphism and haplotype by using the standard TDT method in Haploview(http://www.broad.mit.edu/mpg/haploview/). Results : Through transmission-disequilibrium testing and haplotype analysis, we could not find any statistically significant transmitted allele or haplotype. In addition, a case-control association test with Korean HapMap data did not reveal any statistical significance. Conclusion : Although serotonin-related genes must be considered candidate genes for ASD, we suggest that common SNPs of SLC6A4 are not important markers for associations with Korean ASD.

• Microbiology and Biotechnology Letters
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• v.51 no.1
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• pp.37-42
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• 2023

Neutral and non-essential amino acid, glutamine (Gln), plays an essential role in supplying nitrogen to all the amino acids and nucleotides in the mammalian body. Gln is also the most important carbon source that provides intermediates for gluconeogenesis and fatty acid synthesis and supplements the tricarboxylic acid cycle in fast-growing cancer cells. Among the known 14 Gln transporter genes, soluted carrier family 1 member 5 (SLC1A5) has been reported to be closely associated with cancer cell growth. Three variants (v1, v2, and v3) have been derived from SLC1A5. Here, we established a heterologous gene expression system for the active form of human SLC1A5 variant-2 (hSLC1A5v2) in Escherichia coli. v2 is the smallest variant that has not yet been studied. Four expression systems were investigated: pBAD, pCold, pET, and pQE. We also addressed the problem of codon usage bias. Although pCold and pET overexpressed hSLC1A5v2 in E. coli, they were functionally inactive. hSLC1A5v2 using the pBAD system was able to catalyze the successful transport of Gln, even if it was not highly expressed. Initial activity of hSLC1A5v2 for [¹⁴C] Gln uptake in E. coli reached up to 6.73 μmole·min^-1·gDW^-1 when the cell was induced with 80 mM L-arabinose. In this study, we demonstrated a heterologous expression system for the human membrane protein, SLC1A5, in E. coli. Our results can be used for the functional comparison of SLC1A5 variants (v1, v2, and v3) in future studies, to facilitae the developement of SLC1A5 inhibitors as effective anticancer drugs.

• YAKHAK HOEJI
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• v.54 no.1
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• pp.49-54
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• 2010

SLC6A19 which reported as a neurotransmitter was composed of seven minisatellites. In previous our study, the minisatellites variants of SLC6A19-MS7 showed the susceptibility for hypertension. When this minisatellte sequences were analyzed using the bioinformatic tool, USF1 (upstream transcription factor 1) was found in this region as a putative transcription factor binding site. USF1 is binding with E-boxes which has a consensus sequence of CACGTG. USF1 is a ubiquitously expressed transcription factor and involved in the transcriptional control of many genes including the molecular pathogenesis of cardiovascular disease. Thus, we investigated that the putative functional relationship between the minisatellites variants and susceptibility for myocardial infarction. A case-control study was performed that compared genomic DNA from 400 controls and 225 cases with myocardial infarction. There were no significant differences observed in the overall allelic distribution of minisatellites between controls and cases, which indicates that this polymorphism is not responsible for myocardial infarction susceptibility. Hence, we analyzed the five different minisatellites alleles from this study and characterized 14 different repeats units (Unit1~Unit14). Then, we evaluated the DNA composition, phylogenic tree, and pairwise distances of its repeats. The variability of each repeats differed from 2.33% to 16%. The phylogenic trees for the four SLC6A19-MS7 minisatellites exhibited very different shapes in their braches and distances, and present most common 8 repeats allele was the longest 14 repeats allele. Therefore, this result may help to understand for the evolutional level of the length of minisatellites.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.25 no.2
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• pp.82-88
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• 2014

Objectives : The aim of our study was to investigate association of norepinephrine transporter gene (SLC6A2) polymorphism and side effects of osmotic-release oral system methylphenidate (OROS MPH) in children with attention-deficit hyperactivity disorder (ADHD). Methods : We recruited drug naive children with ADHD (N=97). We administered OROS MPH by tolerable dosage. At week 8 of treatment, parents completed the Barkley's side effect rating scale. We analyzed two SLC6A2 single nucleotide polymorphisms (SNPs), rs192303 and rs3785143, with blood of subjects. We compared the frequency and severity of each side effect among SLC6A2 genotypes of 2 SNPs. Results : In the analysis of frequency of each side effect, irritability differed according to rs192303 and rs3785143 genotype. In comparisons of severity, talking less and disinterest differed according to rs192303 genotype. In the case of rs3785143, severities of disinterest and irritability were involved with genotype. Conclusion : Side effects of OROS MPH showed an association with SLC6A2 genotype.

• Journal of Animal Science and Technology
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• v.51 no.6
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• pp.493-502
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• 2009

Glucose is a major source of metabolic fuel and lipid and protein syntheses. Transport of glucose into the cell is regulated by an action of glucose transport.associated transporters, especially solute carriers 2A (Slc2a, protein symbol GLUT). The present study was focused on examination of mRNA expression of various Slc2a isoforms in the epididymis during postnatal development. Total RNAs isolated from different epididymal segments (caput, corpus, and caudal epididymis) were utilized for real-time polymerase chain reaction analyses. Results showed that Slc2a 1, 3, 4, 5, and 8 were expressed in the entire epididymal regions. In addition, the abundance of these Slc2a isoforms' transcripts was different within each epididymal regions. Moreover, the present study showed differential expression of these Slc2a isoforms among different epididymal segments according to postnatal ages. The current study suggests that glucose transport in the epididymis via various Slc2a isoforms would be necessary for maintenance of the epididymal functions.

• Journal of Genetic Medicine
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• v.19 no.2
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• pp.100-104
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• 2022

The gene encoding solute carrier family 9 member 6 (SLC9A6) on Xq26.3 is associated with Christianson syndrome (CS) mimicking Angelman syndrome. In CS, developmental and epileptic encephalopathy (DEE) appears in about 20%, and DEE with spike-and-wave activation in sleep (SWAS) is reported only in several cases. A 10-year-old boy with DEE showed multidrug resistant focal seizures from 6 months of age. He had progressive microcephaly, regression, global developmental delay without speech, hyperkinesia, and truncal ataxia; he had a long thin face, esotropia, and happy demeanor. Brain magnetic resonance imaging demonstrated cerebellar atrophy. Electroencephalogram at 7.5 years of age showed nearly continuous diffuse paroxysms in slow wave sleep. The seizures were responsive to corticosteroids for a while. Trio whole exome sequencing exhibited a likely pathogenic variant of SLC9A6 in the proband and his asymptomatic mother: c.1194dup (p.Leu399AlafsTer12). This is a rare case report of CS with DEE-SWAS in a Korean patient.

• Clinical and Experimental Pediatrics
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• v.59 no.sup1
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• pp.29-31
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• 2016

Glucose transport 1 (GLUT-1) deficiency is a rare syndrome caused by mutations in the glucose transporter 1 gene (SLC2A1) and is characterized by early-onset intractable epilepsy, delayed development, and movement disorder. De novo mutations and several hot spots in N34, G91, R126, R153, and R333 of exons 2, 3, 4, and 8 of SLC2A1 are associated with this condition. Seizures, one of the main clinical features of GLUT-1 deficiency, usually develop during infancy. Most patients experience brief and subtle myoclonic jerk and focal seizures that evolve into a mixture of different types of seizures, such as generalized tonic-clonic, absence, myoclonic, and complex partial seizures. Here, we describe the case of a patient with GLUT-1 deficiency who developed infantile spasms and showed delayed development at 6 months of age. She had intractable epilepsy despite receiving aggressive antiepileptic drug therapy, and underwent a metabolic workup. Cerebrospinal fluid (CSF) examination showed CSF-glucose-to-blood-glucose ratio of 0.38, with a normal lactate level. Bidirectional sequencing of SLC2A1 identified a missense mutation (c.1198C>T) at codon 400 (p.Arg400Cys) of exon 9.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.8
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• pp.1325-1335
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• 2018

Objective: This study investigated whether spermine supplementation could regulate cell cycle, apoptosis, and amino acid transporter-related genes expression in the thymus and spleen of early weaned piglets. Methods: Eighty female piglets were randomly distributed to receive adequate nutrients supplemented with spermine (0.4 mmol/kg body weight/24 h) or to be provided with restricted nourishment supplemented with normal saline for 7 h or 3, 6, or 9 d in pairs. Results: Regardless of administration time, spermine supplementation significantly up-regulated cyclin A2 gene expression but down-regulated p21 and cyclin D3 mRNA levels in the thymus and spleen and reduced cyclin E2 gene expression in the thymus of piglets (p<0.05). Irrespective of the treatment period, the reduced Bax and caspase-3 gene expressions and improved Bcl-2 mRNA level were observed in the thymus and spleen of spermine-administrated piglets (p<0.05). Regardless of supplementation time, spermine intake significantly enhanced the expressions of amino acid transporter-related genes (SLC1A1, SLC1A5, SLC7A1, SLC7A7, and SLC15A1) in both thymus and spleen, as well as SLC7A9 in the spleen of piglets (p<0.05). In addition, extended spermine administration also markedly promoted cell proliferation, depressed apoptosis and modulated amino acid transport (p<0.05), and such effects were the greatest during prolonged spermine supplementation (6 d) compared to the other time periods (p<0.05). Conclusion: Spermine supplementation may regulate cell cycle during the G1/S phase, suppress apoptosis and modulate amino acid transport. A period of 6 d of spermine supplementation is required to produce the optimal effects on nutritional implications.