PubMed Health⌕ Search

Biomedical subjects

Kyung-Sik Yoon

Publications and source records attributed to Kyung-Sik Yoon.

17 recordsLinked to original sources
PubMed2006

Inhibition of AMP-activated protein kinase suppresses IL-2 expression through down-regulation of NF-AT and AP-1 activation in Jurkat T cells.

AMP-activated protein kinase (AMPK) is a key regulator of energy homeostasis and its activation during T cell receptor stimulation has recently been reported. In this study, we examined the role of AMPK in interleukin (IL)-2 production in T cells. Inhibition of AMPK by compound C, a specific inhibitor of AMPK or small interfering RNA of AMPKalpha1 suppressed IL-2 production in Jurkat T cells and peripheral blood lymphocytes stimulated with PMA plus ionomycin (PMA/Io) or with monoclonal anti-CD3 plus anti-CD28. We then showed that AMPK inhibition reduced PMA/Io-induced IL-2 mRNA expression and IL-2 promoter activation. Moreover, inhibition of AMPK suppressed transcriptional activation of NF-AT and AP-1, but not NF-kappaB, in PMA/Io-activated Jurkat cells. Finally, we found that compound C inhibited PMA/Io-induced phosphorylation of p38, JNK, and GSK-3beta but not of ERK. These results suggest that AMPK mediates IL-2 production by regulating NF-AT and AP-1activation during T cell stimulation.

AMP-Activated Protein Kinases↗
PubMed2006

Tryptophan hydroxylase and serotonin transporter gene polymorphism does not affect the diagnosis, clinical features and treatment outcome of panic disorder in the Korean population.

Panic disorder may be associated with defective serotonin (5-HT) neurotransmission. This study was to investigate the association between the tryptophan hydroxylase (TPH) gene and a serotonin transporter gene promoter polymorphism (5-HTTLPR), with panic disorder in a Korean population. 244 Korean patients with panic disorder and the 227 controls were genotyped by a polymerase chain reaction-based method. The severity of panic disorders was assessed by number of panic attacks during the previous 1 month, as well as scores for anticipatory anxiety, panic distress, and agoraphobic distress, as determined by a visual analogue scale (VAS). All the subjects completed the assessment measures including Spielberger State-Trait Anxiety Inventory-State (STAI-S), Spielberger State-Trait Anxiety Inventory-Trait (STAI-T), Beck Depression Inventory (BDI), Symptom Checklist-90-Revised (SCL-90-R), Revised Anxiety Sensitivity Index (ASI-R), Clinical Global Impression Scale--Severity of Illness (CGI-S), Panic Disorder Severity Scale (PDSS), and the Hamilton Depression Rating Scale (HAMD). Responder analyses were conducted based on changes in CGI-I scores after 10 weeks of treatment. We found no significant differences in the genotype and allele frequencies in TPH A218C and 5-HTTLPR polymorphisms between the panic patients and the control group. Subgroup analyses in terms of comorbidities, response, and other primary clinical variables, indicated no differences in these polymorphisms. Our findings suggest that the TPH A218C polymorphism and 5-HTTLPR play no significant roles in the pathogenesis and clinical symptomatologies, at least in a Korean population.

Age of Onset↗
PubMed2006

BRCA1 and BRCA2 germline mutations in Korean breast cancer patients at high risk of carrying mutations.

We analyzed the mutation spectrum of BRCA1 and BRCA2 genes in 354 Korean breast cancer patients. Overall, 40 patients carried 25 distinct BRCA1/2 mutations including 12 novel mutations. Seven district mutations were found in multiple unrelated patients, with the BRCA2 c.7480C>T mutation detected in eight unrelated patients, accounting for 50% of the mutations detected in BRCA2. The large number (25/40, 62.5%) of recurrent mutations suggests the possibility of developing a simple screening test for these mutations. The frequency of mutations was related to the number and kinds of risk factors, varying from 10.4 to 25% in the five major risk factor groups. The frequency of BRCA mutations in patients with two or more risk factors was markedly higher than that in patients with one risk factor.

BRCA1 Protein↗
PubMed2006

Melatonin stimulates glucose transport via insulin receptor substrate-1/phosphatidylinositol 3-kinase pathway in C2C12 murine skeletal muscle cells.

The prevalence of diabetes has exponentially increased in recent decades due to environmental factors such as nocturnal lifestyle and aging, both of which influence the amount of melatonin produced in the pineal gland. The present study investigated the effect of melatonin on signaling pathways of glucose transport in C2C12 mouse skeletal muscle cells. Intriguingly, treatment of C2C12 cells with melatonin (1 nm) stimulated glucose uptake twofold increase. Melatonin-stimulated glucose transport was inhibited with co-treatment with the melatonin receptor antagonist luzindole. Furthermore, treatment of stably over-expressed melatonin receptor type 2B containing C2C12 myotubes with melatonin amplified glucose transport c. 13-fold. Melatonin also increased the phosphorylation level of insulin receptor substrate-1 (IRS-1) and the activity of phosphoinositide 3-kinase (PI-3-kinase). However, 3',5'-cyclic adenosine monophosphate-activated protein kinase (AMPK), another important glucose transport stimulatory mediator via an insulin-independent pathway, was not influenced by melatonin treatment. Activity of p38 mitogen-activated protein kinase (MAPK), a downstream mediator of AMPK, was also not changed by melatonin. In addition, melatonin increased the expression level of forkhead box A2, which was recently discovered to regulate fatty acid oxidation and to be inhibited by insulin. In summary, melatonin stimulates glucose transport to skeletal muscle cells via IRS-1/PI-3-kinase pathway, which implies, at the molecular level, its role in glucose homeostasis and possibly in diabetes. Additionally, exposure to light at night and aging, both of which lower endogenous melatonin levels may contribute to the incidence and/or development of diabetes.

Biological Transport↗
PubMed2005

Activation of adenosine A3 receptor suppresses lipopolysaccharide-induced TNF-alpha production through inhibition of PI 3-kinase/Akt and NF-kappaB activation in murine BV2 microglial cells.

Adenosine is an endogenous nucleoside that regulates many processes, including inflammatory responses, through activation of its receptors. Adenosine receptors have been reported to be expressed in microglia, which are major immune cells of brain, yet little is known about the role of adenosine receptors in microglial cytokine production. Thus, we investigated the effect of adenosine and adenosine A3 receptor ligands on LPS-induced tumor necrosis factor (TNF-alpha) production and its molecular mechanism in mouse BV2 microglial cells. Adenosine and Cl-IB-MECA, a specific adenosine A3 receptor agonist, suppressed LPS-induced TNF-alpha protein and mRNA levels. Moreover, MRS1523, a selective A3 receptor antagonist, blocked suppressive effects of both adenosine and Cl-IB-MECA on TNF-alpha. We further examined the effect of adenosine on signaling molecules, such as PI 3-kinase, Akt, p38, ERK1/2, and NF-kappaB, which are involved in the regulation of inflammatory responses. Adenosine inhibited LPS-induced phosphatidylinositol (PI) 3-kinase activation and Akt phosphorylation, whereas it had no effect on the phosphorylation of p38 and ERK1/2. We also found that adenosine as well as Cl-IB-MECA inhibited LPS-induced NF-kappaB DNA binding and luciferase reporter activity. Taken together, these results suggest that adenosine A3 receptor activation suppresses TNF-alpha production by inhibiting PI 3-kinase/Akt and NF-kappaB activation in LPS-treated BV2 microglial cells.

Adenosine↗
PubMed2005

AICAR suppresses IL-2 expression through inhibition of GSK-3 phosphorylation and NF-AT activation in Jurkat T cells.

We examined the effect of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), the dephosphorylated form of AICA ribotide (also termed "ZMP"), an intermediate of purine biosynthesis, on interleukin (IL)-2 production in T cells. AICAR inhibited IL-2 production in Jurkat T cells and peripheral blood lymphocytes activated with PMA plus ionomycin (PMA/Io) or with monoclonal anti-CD3 plus anti-CD28. Pretreatment with 5'-iodotubercidin, an adenosine kinase inhibitor, enhanced AICAR suppression of IL-2 production, suggesting that AICAR, not ZMP, is responsible for IL-2 suppression. We then showed that AICAR inhibited PMA/Io-induced IL-2 mRNA expression and IL-2 promoter activation. AICAR inhibited DNA binding and transcriptional activation of NF-AT and to a lesser extent AP-1, but not NF-kappaB, in PMA/Io-activated Jurkat cells. Finally, we found that AICAR inhibited PMA/Io-induced phosphorylation of GSK-3 but not phosphorylation of ERK1/2, p38, and JNK. These results suggest that AICAR exerts its immunosuppressive effect in activated Jurkat cells by inhibiting GSK-3 phosphorylation and NF-AT activation.

Aminoimidazole Carboxamide↗
PubMed2005

Polymorphism in the nuclear factor kappa-B binding promoter region of cyclooxygenase-2 is associated with an increased risk of bladder cancer.

Cyclooxygenase-2 (COX-2) expression is mediated by constitutive nuclear factor (NF)-kappaB. The aim of this study was to investigate the association between the germline alteration of the NF-kappaB binding site of COX-2 and the risk of developing various types of human cancers. Using PCR and DNA sequence analysis, we performed a hospital-based case-control study involving various types of human cancers, namely cervical, breast, lung, and bladder cancer. The COX-2 gene was sequenced in 217 Korean individuals (122 cancer patients; 95 non-cancer patients). We identified 2 novel polymorphisms -1166 C-->G and -1186 T-->G, in the NF-kappaB binding promoter region of COX-2. A polymorphism in nucleotide 1186 was found to be associated with an increased risk of bladder cancer (P=0.038). However, in the case of the other cancers, no significant association was found between polymorphisms in the COX-2 promoter region and the risk of cancer. In conclusion, our results suggest that polymorphisms in nucleotide -1186, which is in the NF-kappaB binding promoter region of the COX-2 gene, may be associated with an increased risk of bladder cancer. Further research is needed to investigate the functional implications of the polymorphisms of the COX-2 promoter gene in human cancer.

Biomarkers, Tumor↗
PubMed2004

The polymorphisms of Tim-1 promoter region are associated with rheumatoid arthritis in a Korean population.

It has been determined that the family of T-cell immunoglobulin domain and mucin domain (TIM) proteins is expressed on T cells. A member of the TIM family, TIM-1, is considered to be a membrane protein associated with the development of Th2-biased immune responses and selectively expressed on Th2 cells. We previously showed that the exon 4 variations of Tim-1 are associated with susceptibility to allergic diseases, as well as autoimmune diseases such as rheumatoid arthritis (RA). In this study, we assessed the association between genotype and allele frequencies of the Tim-1 gene promoter region, in both RA patients and the controls without RA, using polymerase chain reaction-restriction fragment length polymorphism and single-base extension methods. We further investigated the relationships among the genotypes of each polymorphism and C-reactive protein or rheumatoid factor levels in RA patients. The genotype and allele frequencies of the -1637A>G polymorphism in RA patients are significantly different from those in the non-RA controls (P=0.0004 and P=0.001, respectively). Our results strongly suggest that polymorphism in the Tim-1 promoter region might be associated with susceptibility to RA.

Adult↗
PubMed2004

The polymorphisms of Th1 cell surface gene Tim-3 are associated in a Korean population with rheumatoid arthritis.

The family of T-cell immunoglobulin domain and mucin domain (TIM) proteins is identified to be expressed on T cells. A member of TIM family, TIM-3 is selectively expressed on the surface of differentiated Th1 cells. TIM-3 might have an important role in the induction of autoimmune diseases by regulating macrophage activation and interacts with TIM-3 ligand to regulate Th1 responses. In the present study, we analyzed the association of the genotype and allele frequencies between rheumatoid arthritis (RA) patients and the controls without RA using large samples size at the -1516G>T, -574T>G and 4259G>T polymorphic sites of human Tim-3 gene. We further investigated the relationships between the genotypes of each single nucleotide polymorphisms (SNPs) and C-reactive protein (CRP) or rheumatoid factor (RF) levels in RA patients. The genotype and allele frequencies of the -574T>G (P = 0.001 and 0.001, respectively) as well as the 4259G>T (P = 0.001 ands 0.003, respectively) between RA patients and non-RA controls were significantly different. These results strongly suggest that -574T>G and 4259G>T polymorphism of the Tim-3 might be associated with susceptibility to RA.

Adult↗
PubMed2004

The exon 4 variations of Tim-1 gene are associated with rheumatoid arthritis in a Korean population.

The family of T-cell immunoglobulin domain and mucin domain (TIM) proteins is identified to be expressed on T cells. A member of Tim family, TIM-1, is considered as a membrane protein that is associated with the development of Th2 biased immune responses and selectively expressed on Th2 cells. In the present study, we analyzed the association of genotype and allele frequencies between rheumatoid arthritis (RA) patients and the controls without RA using large samples size at 5383_5397del and 5509_5511delCAA variations of Tim-1 gene. We further investigated the relationships among these variations to C-reactive protein (CRP) and rheumatoid factor (RF) levels in RA patients. Although these factors were not associated with exon 4 variations in RA patients, the genotype and allele frequencies of 5383_5397del variation site (P = 0.015 and 0.014, respectively) as well as 5509_5511delCAA variation site (P = 0.0002 and 0.0001, respectively) in RA patients were significantly different from those in the non-RA controls. Our results strongly suggest that the variations of Tim-1 exon 4 might be associated with the susceptibility to RA.

Adult↗
PubMed2004

BRCA1 and BRCA2 germline mutations in Korean patients with sporadic breast cancer.

In order to evaluate the role of BRCA1 and BRCA2 germline mutations in Korean patients with sporadic breast cancer, 97 patients with sporadic breast cancer were analyzed for mutations in the BRCA1 and BRCA2 coding regions, by using a combination of fluorescent-conformation sensitive gel electrophoresis (F-CSGE) and direct sequencing. Fifty-five distinct sequence variants were detected, which included three pathogenic truncating mutations, 15 missense mutations, 16 polymorphisms, and 21 intronic variants. Twenty-six of these variants have never been previously reported and may be of Korean-specific origin. Two pathogenic BRCA1 mutations (c.922_924delinsT, c.5445G>A) and one pathogenic BRCA2 mutation (c.2259delT) were observed, and two of these (BRCA1 c.5445G>A and BRCA2 c.2259delT) are novel. The total prevalence of germline pathogenic mutations in BRCA1 and/or BRCA2 in Korean sporadic breast cancer is estimated to be about 3.1%. Considering that the majority of breast cancer cases are sporadic, the present study will be helpful in the evaluation of the need for the genetic screening of germline BRCA mutations in sporadic breast cancer patients. Further study using a larger sample size is required to determine the merits of genetic diagnosis and counseling in breast cancer patients.

Adult↗
PubMed2004

Combined effect of GSTM1, GSTT1, and COMT genotypes in individual breast cancer risk.

Our previous studies suggested that both catechol O-methyl transferase (COMT) and glutathione S-transferase (GST) M1 and T1 genotypes are associated with breast cancer risk. Here we extended the studies to evaluate the potential combined effect of these genotypes in individual breast cancer risk. Incident breast cancer cases (n = 202) and controls (n = 299) with no previous cancer were recruited from three teaching hospitals in Seoul in 1996-1999. Information on putative risk factors was collected by interviewed questionnaire. PCR-based methods were used for the genotyping analyses. Odds ratios (ORs) and 95% confidence (CIs) intervals were estimated by unconditional logistic regression after adjustment for known or suspected risk factors of breast cancer. Among pre-menopausal women the low activity associated (COMT *L) allele containing genotypes and the GSTM1 null genotype posed increased risks of breast cancer with ORs of 1.7 (95% CI = 1.0 - 2.8) and 1.7 (95% CI = 1.0-2.8), respectively. A marginally significant effect of GSTT1 null genotype was also observed when the total study population was considered (OR = 1.3, 95% CI = 1.0-2.1). When the combined genotype effects were examined, the concurrent lack of GSTM1 and GSTT1 genes posed a more than 2-fold risk of breast cancer (OR = 2.2, 95% CI = 1.2-3.9); this effect was mainly attributable in pre-menopausal women (OR = 3.2, 95% CI = 1.5-7.2). Moreover, the breast cancer risk increased in parallel with the number of COMT , GSTM1 , and GSTT1 at-risk genotypes (p for trend = 0.003). This association was particularly clear in pre-menopausal women among whom combination of all three high-risk genotypes posed a 4.1-fold breast cancer risk (95% CI = 1.4-12.7) compared with pre-menopausal women without at-risk genotypes (p for trend = 0.001). The trend was more pronounced in women with BMI greater than 22 kg/m2 (p for trend < 0.001) and high-risk status of parity factor (nulliparous or women with the first full term pregnancy at age of over 25-year-old) (p for trend = 0.013). These results suggest the combined effect between reproductive factors and GSTM1, GSTT1 and COMT genotypes in human breast carcinogenesis.

Adult↗
PubMed2003

hOGG1 Ser326Cys polymorphism and breast cancer risk among Asian women.

To evaluate the potential association between breast cancer risk and Ser326Cys polymorphism of hOGG1 gene, encoding for an enzyme involved in the base excision repair of 8-hydroxyguanine, hospital based case-control studies were conducted in two Asian populations consisting of 475 breast cancer cases (271 Korean and 204 Japanese) and 500 controls (314 Korean and 186 Japanese). PCR-based methods were employed for the genotyping analyses and the statistical evaluations were performed by unconditional logistic regression model. The frequency of hOGG1 Ser/Ser, Ser/Cys, and Cys/Cys genotypes were 22.5, 48.7, and 28.8% in all cases, and 23.7, 52.1, and 24.1% in the controls. No statistically significant associations between the genotypes and breast cancer risk were observed, neither when the ethnic groups were examined separately nor when the total study population was included. Neither did stratification by menopausal status reveal any association between hOGG1 genotypes and breast cancer. Our novel findings therefore suggest that hOGG1 Ser326Cys polymorphism is unlikely to play a modifying role in individual susceptibility to breast cancer among Asian women.

Adult↗
PubMed2002

Functional catechol-O-methyltransferase gene polymorphism and susceptibility to schizophrenia.

Genetic polymorphism of catechol-O-methyltransferase (COMT), involved in the degradation of catecholamine neurotransmitters, has been investigated as a candidate for modifier of susceptibility to development of schizophrenia. To address this issue further, we carried out a study in Korean schizophrenic patients and controls. The study population consisted of 103 Korean inpatients diagnosed as schizophrenic and their 103 age and sex matched controls. The patients were divided into two groups on the basis of history of aggressive behavior, family history of schizophrenia and related disorders, and age at onset of the disease. The COMT genotypes were determined by a PCR based method. No statistically significant overall associations between the COMT genotypes and risk of schizophrenia were observed. However, subjects with at least one low activity associated COMT-L allele showed a tendency of elevated risk for schizophrenia (OR=1.7, 95% CI=0.9-3.1) compared with those homozygous for the high activity associated COMT-H alleles. Moreover, when cases were stratified by family history of schizophrenia, a significant combined effect was seen: the cases with concurrent family history of schizophrenia and the COMT-L allele containing genotypes had an almost 4-fold (OR=3.9, 95% CI=1.1-14.3) higher risk of schizophrenia compared to controls with the COMT-HH genotypes. Future studies with larger sample sizes are, however, needed to confirm this novel finding.

Adult↗
PubMed2002

Catechol O-methyltransferase genetic polymorphism in panic disorder.

OBJECTIVE: The authors examined the distribution of catechol O-methyltransferase (COMT) genotypes in patients with panic disorder as well as the relationship between a COMT polymorphism and the clinical characteristics of these patients. METHOD: Fifty-one patients with panic disorder and 45 healthy comparison subjects were tested for a genetic polymorphism of COMT. Clinical variables were assessed for the patients with panic disorder. RESULTS: The frequency of the L/L genotype was significantly higher in the patients with panic disorder than in the healthy subjects (19.6% versus 2.2%). Panic disorder was significantly associated with the L allele and L/L genotype. Patients with panic disorder who had the L/L genotype showed poorer treatment response than those with other genotypes. CONCLUSIONS: These results suggest that the L/L genotype of the COMT gene may be related to the development and treatment outcome of panic disorder in some patients.

Adult↗
PubMedDate not supplied

The association between panic disorder and the L/L genotype of catechol-O-methyltransferase.

To clarify the role of catechol-O-methyltransferase (COMT) polymorphism in panic disorder (PD), we investigated a large group of Korean PD patients (N = 178) and controls (N = 182) using a case-control study. We also assessed the response to paroxetine treatment and other clinical variables in the PD patients. The increase in the COMT(L) allele was not statistically significant in PD (p = 0.104). However, compared with the sum of the other genotypes, the frequency of the L/L genotype was significantly higher in PD (p = 0.042). The odd ratios (ORs) also indicated a significant effect of the homozygosity for the COMT(L) allele on an increased risk for PD (OR=2.38; 95% CI 1.03-5.51). In addition, patients with L/L genotype had higher trait-anxiety levels (p = 0.030) and poorer treatment response to paroxetine than those with other genotypes (p = 0.002). Our results suggest that the COMT L/L genotype is associated with PD and the genetic variant of the COMT enzyme may be related to the clinical severity and treatment response to paroxetine in PD.

Adult↗