PER2 is downregulated by the LPS-induced inflammatory response in synoviocytes in rheumatoid arthritis and is implicated in disease susceptibility

Lee, Hwayoung,Nah, Seong-Su,Chang, Sung-Hae,Kim, Hyung-Ki,Kwon, Jun-Tack,Lee, Sanghyun,Cho, Ik-Hyun,Lee, Sang Won,Kim, Young Ock,Hong, Seung-Jae,Kim, Hak-Jae SPANDIDOS PUBLICATIONS 2017 MOLECULAR MEDICINE REPORTS Vol. No.

<P>The clinical symptoms of rheumatoid arthritis (RA) present with circadian variation, with joint stiffness and pain more prominent in the early morning. The mammalian clock genes, which include circadian locomotor output cycles kaput, brain and muscle Arnt-like protein 1, period and cryptochrome, regulate circadian rhythms. In order to identify the association between genetic polymorphisms in the circadian clock gene period 2 (PER2) and RA, the present study genotyped three PER2 single nucleotide polymorphisms (SNPs), rs934945, rs6754875, and rs2304674, using genetic information from 256 RA patients and 499 control subjects. Primary cultured rheumatoid synovial cells were stimulated with 10 mu M lipopolysaccharide (LPS). Total protein was then extracted from the synovial cells following 12 and 24 h, and PER2 protein expression was assayed by immunoblotting. The rs2304674 SNP demonstrated a significant association with susceptibility to RA following Bonferroni correction. However, statistical analysis indicated that the SNPs were not associated with any clinical features of patients with RA. Immunoblotting analysis demonstrated that PER2 protein expression was decreased by LPS-induced inflammation in RA synovial cells; however, this was not observed in normal synovial cells. The results suggest that the PER2 gene may be a risk factor for RA, and expression of the PER2 protein may be affected by inflammation. Therefore, PER2 may contribute to the pathogenesis of RA.</P>

Effects of tianeptine on symptoms of fibromyalgia via BDNF signaling in a fibromyalgia animal model

Hwayoung Lee,Jiyun Im,Hansol Won,Wooyoung Nam,Young Ock Kim,Sang Won Lee,Sanghyun Lee,Ik-Hyun Cho,Hyung-Ki Kim,Jun-Tack Kwon,Hak-Jae Kim 대한생리학회-대한약리학회 2017 The Korean Journal of Physiology & Pharmacology Vol.13 No.1

Previous reports have suggested that physical and psychological stresses may trigger fibromyalgia (FM). Stress is an important risk factor in the development of depression and memory impairments. Antidepressants have been used to prevent stress-induced abnormal pain sensation. Among various antidepressants, tianeptine has been reported to be able to prevent neurodegeneration due to chronic stress and reverse decreases in hippocampal volume. To assess the possible effect of tianeptine on FM symptoms, we constructed a FM animal model induced by restraint stress with intermittent cold stress. All mice underwent nociceptive assays using electronic von Frey anesthesiometer and Hargreaves equipment. To assess the relationship between tianeptine and expression levels of brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and phosphorylated cAMP response element-binding protein (p-CREB), western blotting and immunohistochemistry analyses were performed. In behavioral analysis, nociception tests showed that pain threshold was significantly decreased in the FM group compared to that in the control group. Western blot and immunohistochemical analyses of medial prefrontal cortex (mPFC) and hippocampus showed downregulation of BDNF and p-CREB proteins in the FM group compared to the control group. However, tianeptine recovered these changes in behavioral tests and protein level. Therefore, this FM animal model might be useful for investigating mechanisms linking BDNF-CREB pathway and pain. Our results suggest that tianeptine might potentially have therapeutic efficacy for FM.

Effects of drawing process on the structure and tensile properties of textile-grade PAN fiber and its carbon fiber

Lee, Hwayoung,Lee, Lo-Woon,Lee, Seung-Wook,Joh, Han-Ik,Jo, Seong-Mu,Lee, Sungho Walter de Gruyter GmbH 2014 E-Polymers Vol.14 No.3

<B>Abstract</B><P>Carbon fibers (CFs) were prepared using low-cost, textile-grade polyacrylonitrile fibers, which were 200% to 400% drawn in a hot water bath at 90°C or/and in a tubular furnace at 180°C. X-ray diffractograms confirmed that the drawing process led to higher crystallinity and molecular orientation. These fibers were stabilized in a convection oven at 25-255°C for 390 min. After stabilization, carbonization was performed to obtain carbon fibers. The tensile strength of CFs without drawing was ∼0.8 GPa; however, CFs with 200% and 200% drawing in a hot water bath at 90°C and in a tubular furnace at 180°C, respectively, showed a tensile strength of ∼1.7 GPa. These results suggest that the drawing process of precursor fibers affected the tensile properties of the resulting CFs significantly.</P>

Effects of tianeptine on symptoms of fibromyalgia via BDNF signaling in a fibromyalgia animal model

Lee, Hwayoung,Im, Jiyun,Won, Hansol,Nam, Wooyoung,Kim, Young Ock,Lee, Sang Won,Lee, Sanghyun,Cho, Ik-Hyun,Kim, Hyung-Ki,Kwon, Jun-Tack,Kim, Hak-Jae The Korean Society of Pharmacology 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.4

Previous reports have suggested that physical and psychological stresses may trigger fibromyalgia (FM). Stress is an important risk factor in the development of depression and memory impairments. Antidepressants have been used to prevent stress-induced abnormal pain sensation. Among various antidepressants, tianeptine has been reported to be able to prevent neurodegeneration due to chronic stress and reverse decreases in hippocampal volume. To assess the possible effect of tianeptine on FM symptoms, we constructed a FM animal model induced by restraint stress with intermittent cold stress. All mice underwent nociceptive assays using electronic von Frey anesthesiometer and Hargreaves equipment. To assess the relationship between tianeptine and expression levels of brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and phosphorylated cAMP response element-binding protein (p-CREB), western blotting and immunohistochemistry analyses were performed. In behavioral analysis, nociception tests showed that pain threshold was significantly decreased in the FM group compared to that in the control group. Western blot and immunohistochemical analyses of medial prefrontal cortex (mPFC) and hippocampus showed downregulation of BDNF and p-CREB proteins in the FM group compared to the control group. However, tianeptine recovered these changes in behavioral tests and protein level. Therefore, this FM animal model might be useful for investigating mechanisms linking BDNF-CREB pathway and pain. Our results suggest that tianeptine might potentially have therapeutic efficacy for FM.

Vinyl-Stilbene Inhibits Human Norovirus RNA Replication by Activating Heat-Shock Factor-1

( Ahrim Lee ),( Jieun Sung ),( Dipesh S. Harmalkar ),( Hyeseul Kang ),( Hwayoung Lee ),( Kyeong Lee ),( Choongho Lee ) 한국응용약물학회 2022 Biomolecules & Therapeutics(구 응용약물학회지) Vol.30 No.1

Norovirus (NV) is the most common cause of viral gastroenteritis, with the potential to develop into a fatal disease in those who are immuno-compromised, and effective vaccines and treatments are still non-existent. In this study, we aimed to elucidate the molecular mechanism of the previously identified NV replication inhibitor utilizing a vinyl-stilbene backbone, AC-1858. First, we confirmed the inhibition of the NV RNA replication by a structural analog of AC-1858, AC-2288 with its exclusive cytoplasmic subcellular localization. We further validated the induction of one specific host factor, the phosphorylated form of heat shock factor (HSF)-1, and its increased nuclear localization by AC-1858 treatment. Finally, we verified the positive and negative impact of the siRNA-mediated downregulation and lentivirus-mediated overexpression of HSF-1 on NV RNA replication. In conclusion, these data suggest the restrictive role of the host factor HSF-1 in overall viral RNA genome replication during the NV life cycle.

Design, Synthesis, and Biological Evaluation of Novel Deguelin-Based Heat Shock Protein 90 (HSP90) Inhibitors Targeting Proliferation and Angiogenesis

Chang, Dong-Jo,An, Hongchan,Kim, Kyoung-suk,Kim, Hyun Ho,Jung, Jinkyung,Lee, Jung Min,Kim, Nam-Jung,Han, Young Taek,Yun, Hwayoung,Lee, Sujin,Lee, Geumwoo,Lee, Seungbeom,Lee, Ju Sung,Cha, Jong-Ho,Park, American Chemical Society 2012 Journal of medicinal chemistry Vol.55 No.24

<P>Deguelin exhibits potent apoptotic and antiangiogenic activities in a variety of transformed cells and cancer cells. Deguelin also exhibits potent tumor suppressive effects in xenograft tumor models for many human cancers. Our initial studies confirmed that deguelin disrupts ATP binding to HSP90 and consequently induces destabilization of its client proteins such as HIF-1α. Interestingly, a fluorescence probe assay revealed that deguelin and its analogues do not compete with ATP binding to the N-terminus of HSP90, unlike most HSP90 inhibitors. To determine the key parts of deguelin that contribute to its potent HSP90 inhibition, as well as its antiproliferative and antiangiogenic activities, we have established a structure–activity relationship (SAR) of deguelin. In the course of these studies, we identified a series of novel and potent HSP90 inhibitors. In particular, analogues <B>54</B> and <B>69</B>, the B- and C-ring-truncated compounds, exhibited excellent antiproliferative activities with IC<SUB>50</SUB> of 140 and 490 nM in the H1299 cell line, respectively, and antiangiogenic activities in zebrafish embryos in a dose dependent manner (0.25–1.25 μM).</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jmcmar/2012/jmcmar.2012.55.issue-24/jm301488q/production/images/medium/jm-2012-01488q_0019.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jm301488q'>ACS Electronic Supporting Info</A></P>

Influence of clozapine on neurodevelopmental protein expression and behavioral patterns in animal model of psychiatric disorder induced by low-level of lead

Hwayoung Lee,Minyoung Lee,Hyung-Ki Kim,Young Ock Kim,Jun-Tack Kwon,Hak-Jae Kim 대한약리학회 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.6

Exposure to lead during pregnancy is a risk factor for the development of psychiatric disorders in the offspring. In this study, we investigated whether exposure to low levels of lead acetate (0.2%) in drinking water during pregnancy and lactation causes behavioral impairment and affects the expression of proteins associated with neurodevelopment. Lead exposure altered several parameters in rat offspring compared with those unexposed in open-field, social interaction, and pre-pulse inhibition tests. These parameters were restored to normal levels after clozapine treatment. Western blot and immunohistochemical analyses of the hippocampus revealed that several neurodevelopmental proteins were downregulated in lead-exposed rats. The expression was normalized after clozapine treatment (5 mg/kg/day, postnatal day 35–56). These findings demonstrate that downregulation of several proteins in leadexposed rats affected subsequent behavioral changes. Our results suggest that lead exposure in early life may induce psychiatric disorders and treatment with antipsychotics such as clozapine may reduce their incidence.

Short-Term Hyperhomocysteinemia-Induced Oxidative Stress Activates Retinal Glial Cells and Increases Vascular Endothelial Growth Factor Expression in Rat Retina

LEE, Insun,LEE, Hwayoung,KIM, Ji-Myung,CHAE, Eun Hye,KIM, Soo Jung,CHANG, Namsoo Japan Society for Bioscience, Biotechnology, and A 2007 Bioscience, Biotechnology, and Biochemistry Vol.71 No.5

<P>Hyperhomocysteinemia is associated with an increase in the incidence of vascular diseases, including retinal vascular diseases. We examined the effects of high plasma levels of homocysteine on retinal glial cells and vascular endothelial growth factor (VEGF) expression. Male Sprague-Dawley rats were fed either a 3.0 g/kg homocystine diet or a control diet for 2 week. The homocystine-diet group had higher plasma levels of homocysteine and thiobarbituric acid reactive substances (TBARSs) and lower plasma levels of folate, retinol, α-tocopherol, and retinal expression of CuZn superoxide dismutase (SOD) than the controls. The rats fed the homocystine-diet showed an increase in vimentin, glial fibrillary acidic protein (GFAP), and VEGF immunoreactivity in the retina as compared to the controls. The increase in vimentin immunoreactivity in the hyperhomocysteinemic rats was correlated with changes in GFAP immunoreactivity in astrocytes within the ganglion cell layer. We found for the first time that short-term hyperhomocysteinemia-induced oxidative stress activates retinal glial cells and increases VEGF expression in the retina.</P>

BBOX1 is down-regulated in maternal immune-activated mice and implicated in genetic susceptibility to human schizophrenia

Lee, Hwayoung,Kim, Hyung-Ki,Kwon, Jun-Tack,Park, Shohyun,Park, Hae Jeong,Kim, Su Kang,Park, Jin Kyung,Kang, Won Sub,Kim, Young Jong,Chung, Joo-Ho,Kim, Jong Woo,Kim, Hak-Jae Elsevier 2018 Psychiatry Research Vol.259 No.-

<P><B>Abstract</B></P> <P>Prenatal exposure to infectious or inflammatory insults can increase the risk of developing neuropsychiatric disorders such as bipolar disorder, autism, and schizophrenia in later life. Gamma-butyrobetaine hydroxylase (BBOX 1) is an enzyme responsible for the biosynthesis of l-carnitine, a key molecule in fatty acid metabolism. This cytosolic dimeric protein belongs to the dioxygenase family. In this study, we investigated whether BBOX 1 expression was related to psychiatric disorder in an animal model. We also conducted a case–control study using 284 schizophrenia patients and 409 controls with single-nucleotide polymorphisms (SNPs) in the 5′-near region of BBOX 1. BBOX 1 expression was increased in the medial frontal cortex of a mouse model of schizophrenia induced by maternal immune activation. Furthermore, the genotype and allele frequencies of two SNPs (rs7939644 and rs10767592) were significantly associated with schizophrenia susceptibility. Our results suggest that BBOX 1 might be associated with maternal immune activation and schizophrenia susceptibility. Therefore, it might be involved in the pathophysiology of schizophrenia.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Bbox 1 protein was downregulated in the medial prefrontal cortex in a poly I:C-induced model of schizophrenia. </LI> <LI> Two SNPs of BBOX 1 were associated with human schizophrenia susceptibility. </LI> <LI> Significant pre-pulse facilitation was detected in the poly I:C-induced model. </LI> </UL> </P>

[지상20]Upregulated Trophoblastic Expression of Nuclear Factor-kappa B and LOX-1 in Pregnancy-Induced Hypertension

Hwayoung Lee,Young Mo Ahn,Ho Jin Kim,Hyesook Park,Young Ju Kim 대한체질인류학회 2004 대한체질인류학회 학술대회 연제 초록 Vol.47 No.-