Ferritin heavy chain controls the HIF-driven hypoxic response by activating the asparaginyl hydroxylase FIH

Jin, Peng,Kang, Jengmin,Lee, Myung Kyu,Park, Jong-Wan Elsevier 2018 Biochemical and biophysical research communication Vol.499 No.3

<P><B>Abstract</B></P> <P>Hypoxia-inducible factor 1 (HIF-1) is a key player in cellular response to hypoxia. The stability and transcriptional activity of this protein are oxygen-dependently regulated by the prolyl hydroxylases PHD1-3 and the asparaginyl hydroxylase FIH. Recently, ferritin heavy chain (FTH1) has been characterized to reinforce the HIF-1 signaling pathway in an indirect way through the inhibition of PHD activity by depleting the free iron pool in the cytoplasm. In the present study, we addressed the role of FTH1 in the FIH control of HIF-1 activity. Unexpectedly, immunoprecipitation analyses revealed that FTH1 directly interacted with FIH. In an <I>in vitro</I> hydroxylation assay, FTH1 was found to facilitate the FIH-mediated Asn803 hydroxylation in HIF-1α. As expected, FTH1 prevented the recruitment of p300 to HIF-1α through the Asn803 hydroxylation. In luciferase reporter analyses, FTH1 was found to repress the transcriptional activity of HIF-1α in HCT116 cells under either normoxic or hypoxic conditions. Consequently, FTH1 downregulated the expression of the HIF-1 target genes, such as VEGF, CA9 and GLUT1. Our results suggest a new role of FTH1 as a co-regulator for the FIH-mediated oxygen sensing pathway. Since HIF-1α is involved in pathogenesis of diverse hypoxia-associated diseases, we propose that FTH1 be a potential target in developing new therapeutic strategies against such diseases.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Ferritin Heavy Chain (FTH1) directly interacts with Factor Inhibiting HIF (FIH). </LI> <LI> FTH1 facilitates the FIH-mediated Asn803 hydroxylation in HIF-1α. </LI> <LI> FTH1 prevents the recruitment of p300 to HIF-1α through the Asn803 hydroxylation. </LI> <LI> FTH1 represses the HIF-driven gene expression under either normoxic or hypoxic conditions. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Astrocyte-derived CCL20 reinforces HIF-1-mediated hypoxic responses in glioblastoma by stimulating the CCR6-NF-κB signaling pathway

Jin, Peng,Shin, Seung-Hyun,Chun, Yang-Sook,Shin, Hyun-Woo,Shin, Yong Jae,Lee, Yeri,Kim, Donggeon,Nam, Do-Hyun,Park, Jong-Wan Nature Publishing Group UK 2018 Oncogene Vol.37 No.23

<P>During tumor development, stromal cells are co-opted to the tumor milieu and provide favorable conditions for the tumor. Hypoxia stimulates cancer cells to acquire a more malignant phenotype via activation of hypoxia-inducible factor 1 (HIF-1). Given that cancer cells and astrocytes in glioblastomas coexist in a hypoxic microenvironment, we examined whether astrocytes affect the adaptation of glioblastoma cells to hypoxia. Immunoblotting, reporter assays, quantitative RT-PCR, and chromatin immunoprecipitation were performed to evaluate HIF-1 signaling in glioblastoma cells. Astrocyte-derived chemokine C-C motif ligand 20 (CCL20) was identified using cytokine arrays, and its role in glioblastoma development was evaluated in orthotopic xenografts. Astrocytes augmented HIF-1 alpha expression in glioblastoma cells under hypoxia. The expression of HIF-1 downstream genes, cancer colony formation, and Matrigel invasion of glioblastoma cells were stimulated by conditioned medium from astrocytes pre-exposed to hypoxia. CCL20 was secreted in a hypoxia-dependent manner from astrocytes and busted the hypoxic induction of HIF-1 alpha in glioblastoma cells. Mechanistically, the CCL20/CCR6 signaling pathway upregulates HIF-1 alpha by stimulating nuclear factor kappa B-driven transactivation of the HIF1A gene. Compared with the control tumors, CCR6-deficient glioblastoma xenografts grew more slowly, with poor vascularization, and expressed lower levels of HIF-1 alpha and its downstream proteins. Furthermore, CCR6 expression was correlated with HIF-1 alpha expression in GEO and TCGA datasets from human glioblastoma tissues. These results suggest that glioblastoma cells adapt well to hypoxic stress by virtue of CCL20 derived from neighboring astrocytes.</P>

Foreword to the Special Issue on the Frontiers of IEMS in Asia-Pacific Area

Jin Peng,Takashi Irohara 대한산업공학회 2012 Industrial Engineeering & Management Systems Vol.11 No.2

A Research on Simulated Robot football Match

JinPeng Wang,XueHeng Tao,Xin Zhao,Xiao Liang 한국멀티미디어학회 2006 한국멀티미디어학회 국제학술대회 Vol.2006 No.-

The robot football is a kind of artificial intelligence system based on the un determination system. It gathers new advanced techniques, amusement and game together, thus arousing widespread attention and profound interests. In a simulated robot football match, cooperation of robots as a whole and attack or defense in some certain areas on the field become the key to influence the success of the match. Simulation software of Delphi, VC++6.0 can be used in simulation, this paper attempts introduce the robot football match, taking VC++6.0 as an example.

Modeling Cellular Self-Repair Mechanism under IR Perturbations Based on KTAP Framework

Jinpeng Qi,Yongsheng Ding,Tao Gong,Ying Lin 보안공학연구지원센터 2012 International Journal of Hybrid Information Techno Vol.5 No.2

Brain atlas fusion from high-thickness diagnostic magnetic resonance images by learning-based super-resolution

Zhang, Jinpeng,Zhang, Lichi,Xiang, Lei,Shao, Yeqin,Wu, Guorong,Zhou, Xiaodong,Shen, Dinggang,Wang, Qian Elsevier 2017 Pattern recognition Vol.63 No.-

<P><B>Abstract</B></P> <P>It is fundamentally important to fuse the brain atlas from magnetic resonance (MR) images for many imaging-based studies. Most existing works focus on fusing the atlases from high-quality MR images. However, for low-quality diagnostic images (i.e., with high inter-slice thickness), the problem of atlas fusion has not been addressed yet. In this paper, we intend to fuse the brain atlas from the high-thickness diagnostic MR images that are prevalent for clinical routines. The main idea of our works is to extend the conventional groupwise registration by incorporating a novel super-resolution strategy. The contribution of the proposed super-resolution framework is two-fold. First, each high-thickness subject image is reconstructed to be isotropic by the patch-based sparsity learning. Then, the reconstructed isotropic image is enhanced for better quality through the random-forest-based regression model. In this way, the images obtained by the super-resolution strategy can be fused together by applying the groupwise registration method to construct the required atlas. Our experiments have shown that the proposed framework can effectively solve the problem of atlas fusion from the low-quality brain MR images.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We fuse the brain atlas from real diagnostic MR images with high inter-slice thickness. </LI> <LI> All images are processed through the two-stage learning-based super-resolution. </LI> <LI> Groupwise registration is applied for unbiased atlas fusion. </LI> </UL> </P>

Securing MapReduce Result Integrity via Verification-based Integrity Assurance Framework

Yongzhi Wang,Jinpeng Wei,Yucong Duan 보안공학연구지원센터 2014 International Journal of Grid and Distributed Comp Vol.7 No.6

MapReduce, a large-scale data processing paradigm, is gaining popularity. However, like other distributed computing frameworks, MapReduce suffers from the integrity assurance vulnerability: malicious workers in the MapReduce cluster could tamper with its computation result and thereby render the overall computation result inaccurate. Existing solutions are effective in defeating the malicious behavior of non-collusive workers, but are less effective in detecting collusive workers. In this paper, we propose the Verification-based Integrity Assurance Framework (VIAF). By using task replication and probabilistic result verification, VIAF can detect both non-collusive and collusive workers, even if the malicious workers dominate the environment. We have implemented VIAF on Hadoop, an open source MapReduce implementation. Our theoretical analysis and experimental result show that VIAF can achieve high job accuracy while imposing moderate performance overhead.

Full-state Constraints-based Neuroadaptive Finite-time Control for Induction Motor Drive Systems with Iron Losses

Chen Song,Jinpeng Yu,Lin Zhao,Yumei Ma 제어·로봇·시스템학회 2022 International Journal of Control, Automation, and Vol.20 No.2

This paper proposes a dynamic surface control-based neuroadaptive finite-time control method for induction motors (IMs) with full-state constraints and iron losses. Firstly, the barrier Lyapunov function is introduced to constrain the state variables of IMs, which ensures that the rotor angular velocity and stator current of motor are always in the given range. Secondly, the neural networks (NNs) and dynamic surface control technology are applied to approximate the unknown nonlinear functions and solve the “complexity of differentiation” problem, respectively. Then the finite-time control technology is utilized to accelerate the response speed of the system and realize the fast and effective tracking of the desired signal. At last, the effectiveness of the method is illustrated by simulation results.

Color stability and degradation kinetics of anthocyanins in mulberry stirred yoghurt fermented by different starter cultures

Xin Cheng,Jinpeng Zhu,Zhijie Chen,Zhihao Wu,Fuqiang Zhang,Cai-e Wu,Gong-Jian Fan 한국식품과학회 2023 Food Science and Biotechnology Vol.32 No.10

To evaluate the storage stability of anthocyanin in stirred yoghurt, mulberry juice and different starter cultures (S) were added into milk to investigate the color stability and degradation kinetics of anthocyanin. The result showed that the redness value decreased, while the brightness value increased, and the anthocyanin content decreased significantly from 1.47 ~ 1.86 to 1.01 ~ 1.19 mg/g. The degradation kinetics followed a first-order reaction. Principal component analysis showed that S2 and S6 were correlated with anthocyanins, S8 and S4 were correlated with a*. At the later stage, S4, S8 were correlated with a*, while S2, S4, S6 were correlated with anthocyanins. At 28th day, the anthocyanin content of S4 was 1.14 mg/g, which was not the highest, but the total score was the highest. Therefore, S4 was the best choice when the storage period is 28 days. This study provided technical support for the selection of a better starter for stirring yoghurt.

Exploring differentially expressed genes related to metabolism by RNA-Seq in porcine embryonic fibroblast after insulin treatment

Yingjuan Liang,Jinpeng Wang,Xinyu Li,Shuang Wu,Chaoqian Jiang,Yue Wang,Xuechun Li,Zhong-Hua Liu,Yanshuang Mu 대한수의학회 2022 Journal of Veterinary Science Vol.23 No.6

Background: Insulin regulates glucose homeostasis and has important effects on metabolism, cell growth, and differentiation. Depending on the cell type and physiological context, insulin signal has specific pathways and biological outcomes in different tissues and cells. For studying the signal pathway of insulin on glycolipid metabolism in porcine embryonic fibroblast (PEF), we used high-throughput sequencing to monitor gene expression patterns regulated by insulin. Objectives: The goal of our research was to see how insulin affected glucose and lipid metabolism in PEFs. Methods: We cultured the PEFs with the addition of insulin and sampled them at 0, 48, and 72 h for RNA-Seq analysis in triplicate for each time point. Results: At 48 and 72 h, 801 and 1,176 genes were differentially expressed, respectively. Of these, 272 up-regulated genes and 264 down-regulated genes were common to both time points. Gene Ontology analysis was used to annotate the functions of the differentially expressed genes (DEGs), the biological processes related to lipid metabolism and cell cycle were dominant. And the DEGs were significantly enriched in interleukin-17 signaling pathway, phosphatidylinositol-3-kinase-protein kinase B signaling pathway, pyruvate metabolism, and others pathways related to lipid metabolism by Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Conclusions: These results elucidate the transcriptomic response to insulin in PEF. The genes and pathways involved in the transcriptome mechanisms provide useful information for further research into the complicated molecular processes of insulin in PEF.