Younghoon Kim

Association of the programmed cell death 1 (PDCD1) gene polymorphism with ankylosing spondylitis in the Korean population

The PD-1 (programmed death 1) molecule is a negative regulator of T cells. PDCD1 (programmed cell death 1) has been reported to have a genetic association in systemic lupus erythematosus and rheumatoid arthritis in Caucasians. However, there are no reports on the association between this gene and ankylosing spondylitis (AS). The present study investigated the association of the PD-1 polymorphisms and the haplotypes with AS in a Korean population sample. In a case-control association study, two single-nucleotide polymorphisms, PD-1.5 C/T and PD-1.9 T/C, were genotyped in 95 AS patients and 130 healthy controls. The T allele of the PD-1.9 polymorphism was more frequent in the Korean male population with AS than in the Korean male controls (21.0% versus 6.9%, odds ratio 1.89, 95% confidence interval 1.483 to 2.408). The frequency of the CT haplotype (PD-1.5 C/T and PD-1.9 T/C) was higher in the AS patients (19%) than the controls (5.4%) (odds ratio 1.83, 95% confidence interval 1.559 to 2.521). The PD-1 polymorphism was demonstrated in Korean AS patients. The results suggest a genetic association between the PD-1 polymorphism and susceptibility to AS.

Ischemia-activated microglia induces neuronal injury via activation of gp91phox NADPH oxidase

Although glial cells play a major role in the pathogenesis of many neurological diseases by exacerbating neuronal and non-neuronal cell death, the mechanisms involved are unclear. We examined the effects of microglia-(MCM) or astrocyte-(ACM) conditioned media obtained by chemical ischemia on the neuronal injury in SH-SY5Y cells. Chemical ischemia was induced by the treatment with NaN(3) and 2-deoxy-d-glucose for 2h. MCM-treated SH-SY5Y cells showed reduced the viability, increased caspase-3 activity, decreased Bcl-2/Bax ratio, and increased cytochrome c release, increased inflammatory cytokines, and increased reactive oxygen species (ROS) generation. MCM also increased gp91phox nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which was inhibited by NADPH oxidase inhibitor, apocynin, and gp91phox siRNA. However, ACM did not show any significant changes. The results suggest that microglia activated by ischemic insult may increase reactive oxygen species generation via activation of gp91phox NADPH oxidase, resulting in neuronal injury.

GABAergic synaptic response and its opioidergic modulation in periaqueductal gray neurons of rats with neuropathic pain

BackgroundNeuropathic pain is a chronic and intractable symptom associated with nerve injury. The periaqueductal gray (PAG) is important in the endogenous pain control system and is the main site of the opioidergic analgesia. To investigate whether neuropathic pain affects the endogenous pain control system, we examined the effect of neuropathic pain induced by sacral nerve transection on presynaptic GABA release, the kinetics of postsynaptic GABA-activated Cl- currents, and the modulatory effect of μ-opioid receptor (MOR) activation in mechanically isolated PAG neurons with functioning synaptic boutons.ResultsIn normal rats, MOR activation inhibited the frequency of GABAergic miniature inhibitory postsynaptic currents (mIPSCs) to 81.3% of the control without any alteration in their amplitude. In neuropathic rats, the inhibition of mIPSC frequency by MOR activation was 82.4%. The frequency of GABAergic mIPSCs in neuropathic rats was 151.8% of normal rats without any difference in the mIPSC amplitude. Analysis of mIPSC kinetics showed that the fast decay time constant and synaptic charge transfer of mIPSCs in neuropathic rats were 76.0% and 73.2% of normal rats, respectively.ConclusionsThese results indicate that although the inhibitory effect of MOR activation on presynaptic GABA release is similar in both neuropathic and normal rats, neuropathic pain may inhibit endogenous analgesia in the PAG through an increase in presynaptic GABA release.

Human leukocyte antigen-B*2705 is the predominant subtype in the Korean population with ankylosing spondylitis, unlike in other Asians

This study was performed to investigate the frequency of human leukocyte antigen (HLA)-B27 subtypes in the Korean population with spondyloarthropathy (SpA). We determined the HLA subtypes of 267 SpA patients who were positive for the B27 antigen (as determined by serology) by using a PEL-FREEZ kit (Dynal Biotech, Wisconsin, USA). Clinical features, including sex, peripheral joint involvement, and the presence of uveitis, were analyzed in a retrospective cohort study. Among 267 patients, 244 were B*2705-positive and 22 were B*2704-positive. One patient was positive for B*2704/2705. No other subtype was observed among the analyzed patients. We found that HLA-B*2705 was the predominant subtype in Koreans with SpA; this finding is remarkable because other Asians such as the Han or the Japanese exclusively have the B*2704 subtype. This result suggests that the clinical features and prevalence of SpA in Koreans may be similar to those observed in Europeans.

Screening of Strains with fibrinolytic activity and angiotensin-converting enzyme inhibitory activity from doenjang

As a first step to develop a doenjang possessing functional properties, microbial strains possessing proteolytic activity, fibrinolytic activity, and angiotensin-converting enzyme (ACE) inhibitory activity were screened and isolated from Korean traditional doenjang. First, total 264 isolates showing proteolytic activity were isolated from 14 different doenjang samples. Among them, 4 strains producing both of fibrinolytic activity and ACE inhibitor into the culture medium were selected. The levels of ACE inhibitory effect of G19, G26, P16, and P25 strains were about 82.5, 78.5, 74.5, and 75.6% of inhibition ratio in soybean powder broth, respectively. All isolates were identified as Bacillus amyloliquefaciens based on SDS-PAGE profiles of whole cell proteins and 16S rRNA gene sequence analysis. The result implied that the selected Bacillus strains could be used for the development of doenjang possessing functional properties as potential starter.

Simulation of 1,3-butadiene extractive distillation process using N-methyl-2-pyrrolidone solvent

A computer simulation was performed using a commercial process simulator, Aspen Plus, for NMP (Nmethyl-2-pyrrolidone) extractive distillation process to separate 1,3-butadiene from the C4 hydrocarbon mixtures. The Redlich-Kwong equation of state and NRTL activity coefficient model were used to calculate thermodynamic properties in the simulation of the extractive distillation process. Binary parameters of the NRTL model not provided in the simulator were estimated using the UNIFAC method. The simulation results of the 1,3-butadiene recovery from the C4 mixtures were in good agreement with the plant operation data. The process simulation showed that the material balances in the extractive distillation were successfully predicted for various NMP solvent flow rates. The results obtained in this work provided the optimum solvent rate and the reflux ratio for the NMP extractive distillation process to separate 1,3-butadiene from the C4 mixtures.

Expression and Activity of the Na-K ATPase in Ischemic Injury of Primary Cultured Astrocytes

Astrocytes are reported to have critical functions in ischemic brain injury including protective effects against ischemia-induced neuronal dysfunction. Na-K ATPase maintains ionic gradients in astrocytes and is suggested as an indicator of ischemic injury in glial cells. Here, we examined the role of the Na-K ATPase in the pathologic process of ischemic injury of primary cultured astrocytes. Chemical ischemia was induced by sodium azide and glucose deprivation. Lactate dehydrogenase assays showed that the cytotoxic effect of chemical ischemia on astrocytes began to appear at 2 h of ischemia. The expression of Na-K ATPase α1 subunit protein was increased at 2 h of chemical ischemia and was decreased at 6 h of ischemia, whereas the expression of α1 subunit mRNA was not changed by chemical ischemia. Na-K ATPase activity was time-dependently decreased at 1, 3, and 6 h of chemical ischemia, whereas the enzyme activity was temporarily recovered to the control value at 2 h of chemical ischemia. Cytotoxicity at 2 h of chemical ischemia was significantly blocked by reoxygenation for 24 h following ischemia. Reoxygenation following chemical ischemia for 1 h significantly increased the activity of the Na-K ATPase, while reoxygenation following ischemia for 2 h slightly decreased the enzyme activity. These results suggest that the critical time for ischemia-induced cytotoxicity of astrocytes might be 2 h after the initiation of ischemic insult and that the increase in the expression and activity of the Na-K ATPase might play a protective role during ischemic injury of astrocytes.

Role of nitric oxide and WNK-SPAK/OSR1-KCC2 signaling in daily changes in GABAergic inhibition in the rat dorsal raphe neurons

&NA; Serotonergic neurons in the dorsal raphe nucleus (DRN) act as wake‐inducing neurons in the sleep‐wake cycle and are controlled by gamma‐aminobutyric acid (GABA) synaptic inputs. We investigated daily changes in GABAergic inhibition of the rat DRN neurons and the role of nitric oxide (NO) and cation‐chloride co‐transporters in the GABAergic action. Neuronal NO synthase (nNOS) was co‐expressed in 74% of serotonergic DRN neurons and nNOS expression was higher during daytime (the sleep cycle) than that during nighttime (the wake cycle). GABAergic hyperpolarization of DRN neurons produced by GABAA receptor agonist muscimol was greater and the equilibrium potential of muscimol showed a hyperpolarizing shift during daytime compared to that during nighttime. Expression levels of potassium‐chloride co‐transporter 2 (KCC2) were higher during daytime than that during nighttime, whereas there were no changes in sodium‐potassium‐chloride co‐transporter 1 (NKCC1) expression. With‐no‐lysine kinase (WNK) isoform 1 was more highly expressed during daytime than that during nighttime. Total Ste20‐related proline alanine rich kinase (SPAK) and oxidative stress response kinase 1 (OSR1) were also higher during daytime than during nighttime, while there were no changes in phosphorylated SPAK and OSR1. Consistent with the findings during the sleep‐wake cycle, ex vivo treatment of DRN slices with a NO donor sodium nitroprusside (SNP) increased the expression of KCC2, WNK1, WNK2, WNK3, SPAK, and OSR1, whilst decreasing phosphorylated SPAK. These results suggest that GABAergic synaptic inhibition of DRN serotonergic neurons shows daily changes during the sleep‐wake cycle, which might be regulated by daily changes in nNOS‐derived NO and WNK‐SPAK/OSR1‐KCC2 signaling. HighlightsnNOS was co‐localized in most of TPH‐positive serotonergic neurons in the rat DRN.GABAergic hyperpolarization of DRN neurons showed daily changes.Expression of nNOS and KCC2 was higher during daytime (sleep‐cycle) than nighttime.Expression of WNK1, SPAK, and OSR1 was higher during daytime (sleep‐cycle).Treatment with NO donor increased KCC2, WNK1, WNK2, WNK3, SPAK, and OSR1.