Hepatitis B virus X protein induces lipogenic transcription factor SREBP1 and fatty acid synthase through the activation of nuclear receptor LXRα

Kim, KyeongJin,Kim, Kook Hwan,Kim, Hyeong Hoe,Cheong, JaeHun Portland Press 2008 Biochemical journal Vol.416 No.2

<P>HBV (hepatitis B virus) is a primary cause of chronic liver disease, which frequently results in hepatitis, cirrhosis and ultimately HCC (hepatocellular carcinoma). Recently, we showed that HBx (HBV protein X) expression induces lipid accumulation in hepatic cells mediated by the induction of SREBP1 (sterol-regulatory-element-binding protein 1), a key regulator of lipogenic genes in the liver. However, the molecular mechanisms by which HBx increases SREBP1 expression and transactivation remain to be clearly elucidated. In the present study, we demonstrated that HBx interacts with LXRα (liver X receptor α) and enhances the binding of LXRα to LXRE (LXR-response element), thereby resulting in the up-regulation of SREBP1 and FAS (fatty acid synthase) in the presence or absence of the LXR agonist T0901317 in the hepatic cells and HBx-transgenic mice. Furthermore, HBx also augments the ability to recruit ASC2 (activating signal co-integrator 2), a transcriptional co-activator that controls liver lipid metabolic pathways, to the LXRE with LXRα. These studies place LXRα in a key position within the HBx-induced lipogenic pathways, and suggest a molecular mechanism through which HBV infection can stimulate the SREBP1-mediated control of hepatic lipid accumulation.</P>

Chemokine stromal cell-derived factor-1 induction by C/EBPβ activation is associated with all-<i>trans</i>-retinoic acid-induced leukemic cell differentiation

Kim, KyeongJin,Kim, Hyeong Hoe,Kim, Joon Hong,Choi, Yung Hyun,Kim, Young Hee,Cheong, JaeHun Wiley (John WileySons) 2007 Journal of Leukocyte Biology Vol.82 No.5

Quantitative analysis of NaI(Tl) gamma-ray spectrometry using an artificial neural network

Kim, Jinhwan,Lim, Kyung Taek,Kim, Junhyeok,Kim, Chang-jong,Jeon, Byoungil,Park, Kyeongjin,Kim, Giyoon,Kim, Hojik,Cho, Gyuseong Elsevier BV * North-Holland 2019 Nuclear Instruments & Methods in Physics Research. Vol. No.

<P><B>Abstract</B></P> <P>In this manuscript, we propose an algorithm based on an artificial neural network (ANN) for the analysis of the NaI(Tl) gamma-ray spectra with radioisotope (RI) mixtures to identify RIs and determine the relative activity levels of the identified RIs. The ANN was trained based on the spectra that were generated by synthesizing previously identified spectra from single RIs, considering the characteristics of the measurement environments, such as gain shift effects and statistical fluctuations in the spectrum. The proposed ANN was evaluated through several measured spectra that contained up to six certified reference materials for a quantitative analysis. We also evaluated the shift in the spectra due to temperature variations in the range of 0–50 °C and the low-count spectra with a one-second acquisition period. These results were compared with those from an ANN trained through simulated spectra to emphasize the importance of acquiring a high-quality training dataset. In addition, we show that complex low-resolution spectra can be accurately analyzed with the proposed ANN under various scenarios, in which the maximum root mean square error was found to be 2.8%.</P>

Curcumin inhibits hepatitis C virus replication via suppressing the Akt-SREBP-1 pathway

Kim, KyeongJin,Kim, Kook Hwan,Kim, Hye Young,Cho, Hyun Kook,Sakamoto, Naoya,Cheong, JaeHun Elsevier 2010 FEBS letters Vol.584 No.4

<P><B>Abstract</B></P><P>A polyphenolic compound from the curry spice turmeric, curcumin, is known to show anti-viral activity against the influenza virus, adenovirus, coxsackievirus, and the human immunodeficiency virus. However, it remains to be determined whether curcumin can inhibit the replication of hepatitis C virus (HCV). In this study, we showed that curcumin decreases HCV gene expression via suppression of the Akt-SREBP-1 activation, not by NF-κB pathway. The combination of curcumin and IFNα exerted profound inhibitory effects on HCV replication. Collectively, our results indicate that curcumin can suppress HCV replication in vitro and may be potentially useful as novel anti-HCV reagents.</P>

Evaluation of Serviceability Performance of Void- Free Asphalt Concrete for Heavy Duty Asphalt Pavement

Injung Kim,Kyeongjin Kim,Sungjin Lee,Kwang W. Kim 한국도로학회 2018 한국도로학회 학술대회 발표논문 초록집 Vol.2018 No.05

There are some places such as bridges in the heavily industrialized area where the pavement should have a strong resistance against heavy axle loading and waterproof function. In those places, many polymer-modified asphalt (PMA) pavements were applied to protect premature cracking, severe rutting and water intrusion without success. Therefore, a much tougher pavement material with waterproofing function was developed for those places. This study evaluated important properties of the special type asphalt mixture which is highly condensed to be almost void-free condition. A high-quality PMA binder with PG82-34 grade was used for preparing the mixture and the optimum binder content was determined to allow near 0% air void in the mix design. The deformation strength(SD) by Kim Test and rut depth by wheel tracking test were measured at 60℃ as high temperature properties. The flexural strength and fracture toughness was measured at -10℃ as low temperature property. The void-free AC showed the higher performance in all four properties than any other asphalt concretes which were prepared for comparison. Therefore, it was shown that the normal concern about limiting air voids within 3-5% was just an apprehension. The void-free AC can be applied for heavy duty pavement on the bridge where the water-proofing function and higher rutting and cracking resistance are required.

A sensory-motor neuron type mediates proprioceptive coordination of steering in <i>C</i> . <i>elegans</i> via two TRPC channels

Yeon, Jihye,Kim, Jinmahn,Kim, Do-Young,Kim, Hyunmin,Kim, Jungha,Du, Eun Jo,Kang, KyeongJin,Lim, Hyun-Ho,Moon, Daewon,Kim, Kyuhyung Public Library of Science 2018 PLoS biology Vol.16 No.6

<▼1><P>Animal locomotion is mediated by a sensory system referred to as proprioception. Defects in the proprioceptive coordination of locomotion result in uncontrolled and inefficient movements. However, the molecular mechanisms underlying proprioception are not fully understood. Here, we identify two transient receptor potential cation (TRPC) channels, <I>trp-1</I> and <I>trp-2</I>, as necessary and sufficient for proprioceptive responses in <I>C</I>. <I>elegans</I> head steering locomotion. Both channels are expressed in the SMDD neurons, which are required and sufficient for head bending, and mediate coordinated head steering by sensing mechanical stretches due to the contraction of head muscle and orchestrating dorsal head muscle contractions. Moreover, the SMDD neurons play dual roles to sense muscle stretch as well as to control muscle contractions. These results demonstrate that distinct locomotion patterns require dynamic and homeostatic modulation of feedback signals between neurons and muscles.</P></▼1><▼2><P><B>Author summary</B></P><P>Proprioception provides the nervous system with feedback about body posture in animals and is essential for the generation of coherent locomotive behaviors, such as walking, running, or crawling. However, little is known about the identity of proprioceptive receptors that sense body movement to regulate locomotion and the extent to which proprioception modulates sensorimotor coordination. Here, we analyze the molecular mechanisms that control head steering locomotion of <I>Caenorhabditis elegans</I>. We show that this movement is regulated by the transient receptor potential cation (TRPC) channels TRP-1 and TRP-2 and the SMDD proprioceptive neurons. We observe that mutant animals for both channels are defective in head steering locomotion and that ectopic expression of TRP-1 or TPR-2 in a <I>C</I>. <I>elegans</I> chemosensory neuron confers head bending–dependent responses, suggesting roles for these channels in proprioception. We also find that SMDD neurons are both necessary and sufficient to generate head steering locomotion via the two channels. Moreover, we demonstrate that the proprioceptive system mediates locomotion coordination by desynchronizing activities in motor systems. We conclude that two TRPC channels in collaboration with the proprioceptive receptor SMDD neurons control head steering in worms during forward locomotion.</P></▼2>

The Evolutionarily Conserved LIM Homeodomain Protein LIM-4/LHX6 Specifies the Terminal Identity of a Cholinergic and Peptidergic <i>C</i> . <i>elegans</i> Sensory/Inter/Motor Neuron-Type

Kim, Jinmahn,Yeon, Jihye,Choi, Seong-Kyoon,Huh, Yang Hoon,Fang, Zi,Park, Seo Jin,Kim, Myoung Ok,Ryoo, Zae Young,Kang, Kyeongjin,Kweon, Hee-Seok,Jeon, Won Bae,Li, Chris,Kim, Kyuhyung Public Library of Science 2015 PLoS genetics Vol.11 No.8

<▼1><P>The expression of specific transcription factors determines the differentiated features of postmitotic neurons. However, the mechanism by which specific molecules determine neuronal cell fate and the extent to which the functions of transcription factors are conserved in evolution are not fully understood. In <I>C</I>. <I>elegans</I>, the cholinergic and peptidergic SMB sensory/inter/motor neurons innervate muscle quadrants in the head and control the amplitude of sinusoidal movement. Here we show that the LIM homeobox protein LIM-4 determines neuronal characteristics of the SMB neurons. In <I>lim-4</I> mutant animals, expression of terminal differentiation genes, such as the cholinergic gene battery and the <I>flp-12</I> neuropeptide gene, is completely abolished and thus the function of the SMB neurons is compromised. LIM-4 activity promotes SMB identity by directly regulating the expression of the SMB marker genes via a distinct <I>cis</I>-regulatory motif. Two human LIM-4 orthologs, LHX6 and LHX8, functionally substitute for LIM-4 in <I>C</I>. <I>elegans</I>. Furthermore, <I>C</I>. <I>elegans</I> LIM-4 or human LHX6 can induce cholinergic and peptidergic characteristics in the human neuronal cell lines. Our results indicate that the evolutionarily conserved LIM-4/LHX6 homeodomain proteins function in generation of precise neuronal subtypes.</P></▼1><▼2><P><B>Author Summary</B></P><P>The correct generation and maintenance of the nervous system is critical for the animal’s life. Dysregulation of these processes leads to multiple neurodevelopmental disorders. It has been a daunting challenge not only to identify the developmental mechanisms that determine neuronal cell fate, but also to understand the extent to which the mechanisms are evolutionarily conserved. Here, we describe a developmental mechanism that determines the fate of a specific cholinergic and peptidergic neuronal type in <I>C</I>. <I>elegans</I>. We show that the <I>lim-4</I> LIM homeodomain transcription factor is necessary and sufficient to promote and maintain the specific cholinergic and peptidergic properties and functions via binding to unique DNA sequences. We also demonstrate that <I>C</I>. <I>elegans lim-4</I> and human <I>LHX6</I> show striking functional similarity; specifically, <I>C</I>. <I>elegans</I> LIM-4 or human LHX6 can induce cholinergic and peptidergic characteristics in human neuronal cell lines. Given the high conservation of these transcription factors, these developmental mechanisms are likely to be generally applicable in the nervous system of other organisms as well.</P></▼2>

Sex Differences in Cardiovascular Risk Factors for Dementia

Kim, Mi-Young,Kim, Kyeongjin,Hong, Chang Hyung,Lee, Sang Yoon,Jung, Yi-Sook The Korean Society of Applied Pharmacology 2018 Biomolecules & Therapeutics(구 응용약물학회지) Vol.26 No.6

Dementia, characterized by a progressive cognitive decline and a cumulative inability to behave independently, is highly associated with other diseases. Various cardiovascular disorders, such as coronary artery disease and atrial fibrillation, are well-known risk factors for dementia. Currently, increasing evidence suggests that sex factors may play an important role in the pathogenesis of diseases, including cardiovascular disease and dementia. Recent studies show that nearly two-thirds of patients diagnosed with Alzheimer's disease are women; however, the incidence difference between men and women remains vague. Therefore, studies are needed to investigate sex-specific differences, which can help understand the pathophysiology of dementia and identify potential therapeutic targets for both sexes. In the present review, we summarize sex differences in the prevalence and incidence of dementia by subtypes. This review also describes sex differences in the risk factors of dementia and examines the impact of risk factors on the incidence of dementia in both sexes.

Prolyl hydroxylation primes CMGC kinases for activation through Tyrosine autophosphorylation

KyeongJin Kim,Chung Kwon Kim,Sang Bae Lee 한국실험동물학회 2022 한국실험동물학회 학술발표대회 논문집 Vol.2022 No.7

The orphan nuclear receptor SHP inhibits apoptosis during the monocytic differentiation by inducing p21WAF1

KyeongJin Kim,Yoon Ha Choi,김형회,정재훈 생화학분자생물학회 2009 Experimental and molecular medicine Vol.41 No.6

Small heterodimer partner (SHP) is an atypical member of nuclear receptor superfamily that lacks a DNA-binding domain. In previous study, we showed that SHP, c-jun, p65 of NF-κB subunits, and p21WAF1 expression was increased during monocytic differentiaton with the exposure of human leukemia cells to a differentiation agent, PMA. In this study, c-Jun and p65 were shown to mediate the transcriptional activation of the SHP promoter. In addition, SHP induced the cell cycle regulatory protein levels and cooperatively increased an induction of p21WAF1 expression with p65. Furthermore, SHP protected differentiated cells from etoposide-induced cellular apoptosis through the induction and cytoplasmic sequestration of p21WAF1. Complex formation between SHP and p21WAF1 was demonstrated by means of coimmunoprecipitation. These results suggest that SHP prolongs a cellular survival of differentiating monocytes through the transcriptional regulation of target genes of cell survival and differentiation.