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Jing-Si Herbal Tea Suppresses H2O2-Instigated Inflammation and Apoptosis by Inhibiting Bax and Mitochondrial Cytochrome C Release in HIG-82 Synoviocytes

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Environmental Toxicology 2024年第12期39卷 5347-5356页

作者： Kao, Shih-Wen Chang, Yu-Chun Lin, Feng-Huei Huang, Tai-Lung Chen, Tung-Sheng Lin, Shinn-Zong Lin, Kuan-Ho Kuo, Wei-Wen Ho, Tsung-Jung Huang, Chih-Yang Graduate Institute of Aging Medicine China Medical University Taichung Taiwan Department of Orthopedic Surgery Chung-Shan Medical University Hospital Taichung Taiwan Department of Biological Science and Technology College of Life Sciences China Medical University Taichung Taiwan Cardiovascular and Mitochondrial Related Disease Research Center Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan Institute of Biomedical Engineering College of Medicine and College of Engineering National Taiwan University Taipei Taiwan Division of Biomedical Engineering and Nanomedicine Research National Health Research Institute Miaoli Taiwan Department of Orthopedics Chung-Kang Branch Cheng Ching General Hospital Taichung Taiwan School of Life Science National Taiwan Normal University Taipei Taiwan Department of Neurosurgery Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan Bioinnovation Center Buddhist Tzu Chi Medical Foundation Hualien Taiwan Department of Emergency Medicine China Medical University Hospital Taichung Taiwan College of Medicine China Medical University Taichung Taiwan Ph.D. Program for Biotechnology Industry China Medical University Taichung Taiwan School of Pharmacy China Medical University Taichung Taiwan School of Post-Baccalaureate Chinese Medicine College of Medicine Tzu chi University Hualien Taiwan Department of Chinese Medicine Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Tzu Chi University Hualien Taiwan Integration Center of Traditional Chinese and Modern Medicine Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan Department of Medical Laboratory Science and Biotechnology Asia University Taichung Taiwan

Inflammation is an intrinsic protective mechanism against various forms of cellular injuries in humans;however, its undesired activation results in tissue damage and cell death. The onset of chronic inflammation and oxidative stress are the key characteristics of autoimmune inflammatory diseases such as rheumatoid arthritis (RA), for which an effective treatment is yet to be developed. Therefore, in this study, we investigated the protective effects and molecular mechanisms of a novel herbal preparation, Jing-Si herbal tea (JS), against H2O2-induced inflammation and cellular damage in HIG-82 synoviocytes. We found that JS did not show any significant alterations in cell viability at 2O2-induced pathological oxidative stress (ROS) in HIG-82 cells. Interestingly, JS treatment not only reduced the ROS levels but also significantly repressed the protein expressions of collagen degrading proteases in a dose-dependent manner. Treatment with JS showed enhanced cell viability against H2O2-induced toxic ROS levels. The expressions of cell protective aggrecan, Collagen II, and Bcl-2 were increased, whereas MMP-13, ADAMTS-2, Cytochrome C, and cleaved Caspase 3 were decreased by JS under inflammatory agents H2O2, MIA, LPS, and TNF-α treatment, respectively, in HIG-82 cells. Interestingly, the cytoprotective effect of JS treatment was attributed to a decreased mitochondrial localization of Bax and a reduction of Cytochrome C release into the cytoplasm of H2O2-treated HIG-82 cells. Collectively, our results suggest a novel protective mechanism of JS for RA treatment, which could be potentially applied as a complementary treatment or as an alternative therapeutic approach to mitigate inflammatory diseases. © 2024 Wiley Periodicals LLC.

关键词： Cell death

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A Medicinal Chemistry Perspective on Excitatory Amino Acid Transporter 2 Dysfunction in Neurodegenerative Diseases(vol 66, pg 2330, 2023)

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JOURNAL OF MEDICINAL CHEMISTRY 2023年第4期66卷 2330-2346页

作者： Fontana, Igor C. Souza, Debora G. Souza, Diogo O. Gee, Antony Zimmer, Eduardo R. Bongarzone, Salvatore School of Biomedical Engineering and Imaging Sciences St Thomas’ Hospital King’s College London London SE1 7EH United Kingdom Graduate Program in Biological Sciences: Biochemistry Universidade Federal do Rio Grande do Sul Rua Ramiro Barcelos 2600 90035-003 Porto Alegre Brazil Division of Clinical Geriatrics Center for Alzheimer Research Department of Neurobiology Care Sciences and Society Karolinska Institutet Blickagången 16 - Neo floor seventh 141 83 Stockholm Sweden Brain Institute of Rio Grande do Sul Pontifical Catholic University of Rio Grande do Sul Av. Ipiranga 6681 Porto Alegre Brazil Department of Biochemistry Universidade Federal do Rio Grande do Sul Rua Ramiro Barcelos 2600 90035-003 Porto Alegre Brazil Department of Pharmacology Universidade Federal do Rio Grande do Sul Av. Sarmento Leite 500 sala 90035-003 Porto Alegre Brazil Graduate Program in Biological Sciences: Biochemistry (PPGBioq) and Pharmacology and Therapeutics (PPGFT) Universidade Federal do Rio Grande do Sul Av. Sarmento Leite 500 sala 305 Porto Alegre Brazil McGill University Research Centre for Studies in Aging McGill University Montreal Quebec H4H 1R3 Canada

The excitatory amino acid transporter 2 (EAAT2) plays a key role in the clearance and recycling of glutamate - the major excitatory neurotransmitter in the mammalian brain. EAAT2 loss/dysfunction triggers a cascade of neurodegenerative events, comprising glutamatergic excitotoxicity and neuronal death. Nevertheless, our current knowledge regarding EAAT2 in neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD), is restricted to post-mortem analysis of brain tissue and experimental models. Thus, detecting EAAT2 in the living human brain might be crucial to improve diagnosis/therapy for ALS and AD. This perspective article describes the role of EAAT2 in physio/pathological processes and provides a structure–activity relationship of EAAT2-binders, bringing two perspectives: therapy (activators) and diagnosis (molecular imaging tools).

关键词： Central nervous system Monomers Peptides and proteins Rodent models Selectivity

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OXidative Stress PREDictor: A Supervised Learning Approach for Annotating Cellular Oxidative Stress States in Inflammatory Cells

Advanced Intelligent Systems

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Advanced Intelligent Systems 2025年第3期7卷

作者： Chen, Po-Yuan Ko, Tai-Ming Institute of Bioinformatics and Systems Biology College of Engineering Bioscience National Yang Ming Chiao Tung University Hsinchu300 Taiwan Bioinformatics Program Institute of Statistical Science Taiwan International Graduate Program Academia Sinica Taipei115 Taiwan Institute of Biomedical Sciences Academia Sinica Taipei115 Taiwan Institute of Statistical Science Academia Sinica Taipei115 Taiwan Department of Biological Science and Technology College of Engineering Bioscience National Yang Ming Chiao Tung University Hsinchu300 Taiwan National Yang Ming Chiao Tung University Hsinchu300 Taiwan School of Pharmacy College of Pharmacy Drug Development and Value Creation Research Center Kaohsiung Medical University Kaohsiung807 Taiwan

Oxidative stress, characterized by an imbalance between reactive oxygen species (ROS) and antioxidants, plays a pivotal role in inflammatory responses associated with both chronic diseases and acute injuries. In this study, OXidative Stress PREDictor (OxSpred), a supervised learning model tailored to accurately annotate the oxidative stress state of innate immune cells at the single-cell level, is introduced. Compared to the traditional gene-set-variation-analysis-based enrichment method, OxSpred demonstrates superior accuracy with an area under the receiver operating characteristic curve of 0.89 and offers interpretable embeddings with significant biological relevance. Using the predicted ROS states, precise elucidation and interpretation of the roles of novel innate immune cell subtypes can be achieved. Overall, OxSpred enhances the utility of single-cell transcriptomic datasets by providing a robust in silico method for determining intracellular oxidative stress states, thereby enriching the understanding of innate immune cell functions during inflammation. © 2024 The Author(s). Advanced Intelligent Systems published by Wiley-VCH GmbH.

关键词： Cells

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Technology Roadmap for Flexible Sensors

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ACS NANO 2023年第6期17卷 5211-5295页

作者： Luo, Yifei Abidian, Mohammad Reza Ahn, Jong-Hyun Akinwande, Deji Andrews, Anne M. Antonietti, Markus Bao, Zhenan Berggren, Magnus Berkey, Christopher A. Bettinger, Christopher John Chen, Jun Chen, Peng Cheng, Wenlong Cheng, Xu Choi, Seon-Jin Chortos, Alex Dagdeviren, Canan Dauskardt, Reinhold H. Di, Chong-an Dickey, Michael D. Duan, Xiangfeng Facchetti, Antonio Fan, Zhiyong Fang, Yin Feng, Jianyou Feng, Xue Gao, Huajian Gao, Wei Gong, Xiwen Guo, Chuan Fei Guo, Xiaojun Hartel, Martin C. He, Zihan Ho, John S. Hu, Youfan Huang, Qiyao Huang, Yu Huo, Fengwei Hussain, Muhammad M. Javey, Ali Jeong, Unyong Jiang, Chen Jiang, Xingyu Kang, Jiheong Karnaushenko, Daniil Khademhosseini, Ali Kim, Dae-Hyeong Kim, Il-Doo Kireev, Dmitry Kong, Lingxuan Lee, Chengkuo Lee, Nae-Eung Lee, Pooi See Lee, Tae-Woo Li, Fengyu Li, Jinxing Liang, Cuiyuan Lim, Chwee Teck Lin, Yuanjing Lipomi, Darren J. Liu, Jia Liu, Kai Liu, Nan Liu, Ren Liu, Yuxin Liu, Yuxuan Liu, Zhiyuan Liu, Zhuangjian Loh, Xian Jun Lu, Nanshu Lv, Zhisheng Magdassi, Shlomo Malliaras, George G. Matsuhisa, Naoji Nathan, Arokia Niu, Simiao Pan, Jieming Pang, Changhyun Pei, Qibing Peng, Huisheng Qi, Dianpeng Ren, Huaying Rogers, John A. Rowe, Aaron Schmidt, Oliver G. Sekitani, Tsuyoshi Seo, Dae-Gyo Shen, Guozhen Sheng, Xing Shi, Qiongfeng Someya, Takao Song, Yanlin Stavrinidou, Eleni Su, Meng Sun, Xuemei Takei, Kuniharu Tao, Xiao-Ming Tee, Benjamin C. K. Thean, Aaron Voon-Yew Trung, Tran Quang Wan, Changjin Wang, Huiliang Wang, Joseph Wang, Ming Wang, Sihong Wang, Ting Wang, Zhong Lin Weiss, Paul S. Wen, Hanqi Xu, Sheng Xu, Tailin Yan, Hongping Yan, Xuzhou Yang, Hui Yang, Le Yang, Shuaijian Yin, Lan Yu, Cunjiang Yu, Guihua Yu, Jing Yu, Shu-Hong Yu, Xinge Zamburg, Evgeny Zhang, Haixia Zhang, Xiangyu Zhang, Xiaosheng Zhang, Xueji Zhang, Yihui Zhang, Yu Zhao, Siyuan Zhao, Xuanhe Zheng, Yuanjin Zheng, Yu-Qing Zheng, Zijian Zhou, Tao Zhu, Bowen Zhu, Ming Zhu, Rong Zhu, Yangzhi Zhu, Yong Zou, Guijin Chen, Xiaodong 08-03 Innovis Singapore 138634 Republic of Singapore Innovative Centre for Flexible Devices (iFLEX) School of Materials Science and Engineering Nanyang Technological University Singapore 639798 Singapore Department of Biomedical Engineering University of Houston Houston Texas 77024 United States School of Electrical and Electronic Engineering Yonsei University Seoul 03722 Republic of Korea Department of Electrical and Computer Engineering The University of Texas at Austin Austin Texas 78712 United States Microelectronics Research Center The University of Texas at Austin Austin Texas 78758 United States Department of Chemistry and Biochemistry California NanoSystems Institute and Department of Psychiatry and Biobehavioral Sciences Semel Institute for Neuroscience and Human Behavior and Hatos Center for Neuropharmacology University of California Los Angeles Los Angeles California 90095 United States Colloid Chemistry Department Max Planck Institute of Colloids and Interfaces 14476 Potsdam Germany Department of Chemical Engineering Stanford University Stanford California 94305 United States Laboratory of Organic Electronics Department of Science and Technology Campus Norrköping Linköping University 83 Linköping Sweden Wallenberg Initiative Materials Science for Sustainability (WISE) and Wallenberg Wood Science Center (WWSC) SE-100 44 Stockholm Sweden Department of Materials Science and Engineering Stanford University Stanford California 94301 United States Department of Biomedical Engineering and Department of Materials Science and Engineering Carnegie Mellon University Pittsburgh Pennsylvania 15213 United States Department of Bioengineering University of California Los Angeles Los Angeles California 90095 United States School of Chemistry Chemical Engineering and Biotechnology Nanyang Technological University Singapore 637457 Singapore Nanobionics Group Department of Chemical and Biological Engineering Monash University Clayton Australia 3800 Monash

Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze continued...challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative

关键词： soft materials mechanics engineering flexible electronics conformable sensors bioelectronics human-machine interfaces body area sensor networks technology translation sustainable electronics

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Membrane Protein Modification Modulates Big and Small Extracellular Vesicle Biodistribution and Tumorigenic Potential in Breast Cancers In Vivo

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Advanced Materials 2023年第13期35卷 e2208966页

作者： Magoling, Bryan John Abel Wu, Anthony Yan-Tang Chen, Yen-Ju Wong, Wendy Wan-Ting Chuo, Steven Ting-Yu Huang, Hsi-Chien Sung, Yun-Chieh Hsieh, Hsin Tzu Huang, Poya Lee, Kang-Zhang Huang, Kuan-Wei Chen, Ruey-Hwa Chen, Yunching Lai, Charles Pin-Kuang Institute of Atomic and Molecular Sciences Academia Sinica Taipei10617 Taiwan Graduate Institute of Biochemical Sciences National Taiwan University Taipei10617 Taiwan Chemical Biology and Molecular Biophysics Program TIGP Academia Sinica Taipei11529 Taiwan Department of Pharmacology College of Medicine National Taiwan University Taipei100233 Taiwan Institute of Biomedical Engineering and Frontier Research Center on Fundamental and Applied Sciences of Matters National Tsing Hua University Hsinchu30013 Taiwan Department of Chemical Engineering National Tsing Hua University Hsinchu30013 Taiwan Institute of Biological Chemistry Academia Sinica Taipei11529 Taiwan Genome and Systems Biology Degree Program National Taiwan University Taipei10617 Taiwan

Extracellular vesicles (EVs) are released by cells to mediate intercellular communication under pathological and physiological conditions. While small EVs (sEVs;200 nm, microvesicles) are less well explored. Here, bEVs and sEVs are identified as distinct EV populations, and it is determined that bEVs are released in a greater bEV:sEV ratio in the aggressive human triple-negative breast cancer (TNBC) subtype. PalmGRET, bioluminescence-resonance-energy-transfer (BRET)-based EV reporter, reveals dose-dependent EV biodistribution at nonlethal and physiological EV dosages, as compared to lipophilic fluorescent dyes. Remarkably, the bEVs and sEVs exhibit unique biodistribution profiles, yet individually promote in vivo tumor growth in a syngeneic immunocompetent TNBC breast tumor murine model. The bEVs and sEVs share mass-spectrometry-identified tumor-progression-associated EV surface membrane proteins (tpEVSurfMEMs), which include solute carrier family 29 member 1, Cd9, and Cd44. tpEVSurfMEM depletion attenuates EV lung organotropism, alters biodistribution, and reduces protumorigenic potential. This study identifies distinct in vivo property and function of bEVs and sEVs in breast cancer, which suggest the significant role of bEVs in diseases, diagnostic and therapeutic applications. © 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.

关键词： Mass spectrometry

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Functional neuroplasticity of facilitation and interference effects on inhibitory control following 3-month physical exercise in aging

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Scientific Reports 2024年第1期14卷 1-13页

作者： Wu, Hong-Yi Huang, Chih-Mao Hsu, Ai-Ling Chen, Chiao-Nan Wu, Changwei W. Chen, Jyh-Horng Graduate Institute of Biomedical Electronics and Bioinformatics National Taiwan University Taipei Taiwan Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu Taiwan Bachelor Program in Artificial Intelligence Chang Gung University Taoyuan Taiwan Department of Psychiatry Chang Gung Memorial Hospital at Linkou Taoyuan Taiwan Department of Physical Therapy and Assistive Technology National Yang Ming Chiao Tung University Taipei Taiwan Graduate Institute of Mind Brain and Consciousness Taipei Medical University New Taipei Taiwan Research Center of Sleep Medicine Taipei Medical University Hospital Taipei Taiwan Department of Electrical Engineering National Taiwan University Taipei Taiwan

Preservation of executive function, like inhibition, closely links to the quality of life in senior adults. Although neuroimaging literature has shown enhanced inhibitory function followed by aerobic exercise, current evidence implies inconsistent neuroplasticity patterns along different time durations of exercise. Hence, we conducted a 12-week exercise intervention on 12 young and 14 senior volunteers and repeatedly measured the inhibitory functionality of distinct aspects (facilitation and interference effects) using the numerical Stroop task and functional Magnetic Resonance Imaging. Results showcased improved accuracy and reduced reaction times (RT) after 12-week exercise, attributed to frontoparietal and default mode network effects. In young adults, the first phase (0 to six weeks) exercise increased the activation of the right superior medial frontal gyrus, associated with reduced RT in interference, but in the second intervention phase (six to twelve weeks), the decreased activation of the left superior medial frontal gyrus positively correlated with reduced RT in facilitation. In senior adults, the first six-week intervention led to reduced activations of the inferior frontal gyrus, inferior parietal gyrus, and default mode network regions, associated with the reduced RT in interference. Still, in the second intervention phase, only the visual area exhibited increased activity, associated with reduced RT in interference. Except for the distinctive brain plasticity between the two phases of exercise intervention, the between-group comparison also presented that the old group gained more cognitive benefits within the first six weeks of exercise intervention;however, the cognitive improvements in the young group occurred after six weeks of intervention. Limited by the sample size, these preliminary findings corroborated the benefits of aerobic exercise on the inhibitory functions, implying an age × exercise interaction on the brain plasticity for both facilita

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Modeling BOLD-fMRI Hemodynamics via Multidimensional Decomposition of Electrophysiology Data: A Simulation Study

Modeling BOLD-fMRI Hemodynamics via Multidimensional Decompo...

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Annual International Conference of the IEEE engineering in Medicine and Biology Society (EMBC)

作者： Dylan W. Mann-Krzisnik Georgios D. Mitsis Graduate Program in Biological and Biomedical Engineering (BBME) McGill University Montréal QC Canada Department of Bioengineering McGill University Montréal QC Canada

ISBN: (数字)9781728119908

ISBN: (纸本)9781728119915

We propose a framework for studying the electrophysiological correlates of BOLD-fMRI. This framework relies on structured coupled matrix-tensor factorization (sCMTF), a joint multidimensional decomposition which reveals dynamical interactions between LFP/EEG oscillatory features and BOLD-fMRI data. We test whether LFP/EEG-BOLD co-fluctuations and regional hemodynamic response functions can be estimated by sCMTF using whole-brain modelling of restingstate activity. We produce permuted datasets to show that our framework extracts EEG/LFP temporal patterns that correlate significantly with BOLD signal fluctuations. Our framework is also capable of estimating HRFs that accurately embodies simulated hemodynamics, with a word of caution regarding initialization of the sCMTF algorithm.

关键词： Brain modeling Electroencephalography Optical fibers Oscillators Data models Frequency modulation Time-frequency analysis

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Correction: Reconsidering invasion history of common land snails in Japan through genome-wide analyses

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biological Invasions 2023年第11期25卷 3551-3552页

作者： Hirano, Takahiro Yamazaki, Daishi Ito, Shun Sato, Mitsuhiko P. Matsuo, Ayumi Saito, Takumi Nishi, Hirotaka Ye, Bin Dong, Zhengzhong Van Tu, Do Shau-Hwai, Aileen Tan Suyama, Yoshihisa Chiba, Satoshi Center for Northeast Asian Studies Tohoku University Sendai Japan Graduate School of Life Sciences Tohoku University Sendai Japan Biology Program Faculty of Science University of the Ryukyus Okinawa Japan Faculty of Agriculture and Marine Science Kochi University Nankoku Japan Department of Environmental Science Faculty of Science Toho University Funabashi Japan Kazusa DNA Research Institute Kisarazu Japan Kawatabi Field Science Center Graduate School of Agricultural Science Tohoku University Osaki Japan Department of Botany and Zoology Faculty of Science Masaryk University Brno Czech Republic Toyohashi Museum of Natural History Toyohashi Japan Institute of Biomedical and Health Engineering Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Shenzhen China Agricultural Experiment Station Zhejiang University Hangzhou China Institute of Ecology and Biological Resources Vietnam Academy of Science and Technology Hanoi Vietnam Graduate University of Science and Technology Vietnam Academy of Science and Technology Hanoi Vietnam School of Biological Sciences Universiti Sains Malaysia Penang Malaysia Centre for Marine and Coastal Studies Universiti Sains Malaysia Penang Malaysia

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Endogenous opioid signaling in the retina modulates sleep/wake activity in mice

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Neurobiology of Sleep and Circadian Rhythms 2022年 13卷 100078页

作者： Berezin, Casey-Tyler Bergum, Nikolas Luchini, Kes A. Curdts, Sierra Korkis, Christian Vigh, Jozsef Cell and Molecular Biology Graduate Program Colorado State University 1005 Campus Delivery Fort Collins 80523 CO United States Department of Biomedical Sciences Colorado State University 1601 Campus Delivery Fort Collins 80523 CO United States Department of Chemical and Biological Engineering Walter Scott Jr. College of Engineering Colorado State University 1376 Campus Delivery Fort Collins 80523 CO United States

Circadian sleep/wake rhythms are synchronized to environmental light/dark cycles in a process known as photoentrainment. We have previously shown that activation of β-endorphin-preferring μ-opioid receptors (MORs) inhibits the light-evoked firing of intrinsically photosensitive retinal ganglion cells (ipRGCs), the sole conduits of photoentrainment. Although we have shown that β-endorphin is expressed in the adult mouse retina, the conditions under which β-endorphin is expressed are unknown. Moreover, it is unclear whether endogenous activation of the MORs expressed by ipRGCs modulates the photoentrainment of sleep/wake cycles. To elucidate this, we first measured the mRNA expression of β-endorphin's precursor, proopiomelanocortin (POMC), at various times of day by quantitative reverse-transcription PCR. POMC mRNA appears to have cyclic expression in the mouse retina. We then studied β-endorphin expression with immunohistochemistry and found that retinal β-endorphin is more highly expressed in the dark/at night. Finally, we used telemetry to measure activity, EEG and EMG in freely moving animals to compare sleep/wake cycles in wild-type and transgenic mice in which only ipRGCs lack functional MORs. Results from these experiments suggest that the MORs expressed by ipRGCs contribute to the induction and maintenance of activity in the dark phase in nocturnal mice, via the promotion of wakefulness and inhibition of slow-wave sleep. Together, these data suggest that endogenous β-endorphin activates MORs expressed by ipRGCs to modulate sleep/wake activity via the photoentrainment pathway. © 2022 The Authors

关键词： Proopiomelanocortin Retina Sleep/wake Telemetry β-endorphin μ-Opioid receptor

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Structural basis and synergism of ATP and Na⁺ activation in bacterial K⁺ uptake system KtrAB

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Nature Communications 2024年第1期15卷 3850页

作者： Chiang, Wesley Tien Chang, Yao-Kai Hui, Wei-Han Chang, Shu-Wei Liao, Chen-Yi Chang, Yi-Chuan Chen, Chun-Jung Wang, Wei-Chen Lai, Chien-Chen Wang, Chun-Hsiung Luo, Siou-Ying Huang, Ya-Ping Chou, Shan-Ho Horng, Tzyy-Leng Hou, Ming-Hon Muench, Stephen P. Chen, Ren-Shiang Tsai, Ming-Daw Hu, Nien-Jen Graduate Institute of Biochemistry National Chung Hsing University Taichung 402202 Taiwan Institute of Biological Chemistry Academia Sinica Taipei 115201 Taiwan Department of Civil Engineering National Taiwan University Taipei 106319 Taiwan Department of Biomedical Engineering National Taiwan University Taipei 10663 Taiwan Life Science Group Scientific Research Division National Synchrotron Radiation Research Center Hsinchu 30092 Taiwan Institute of Molecular Biology National Chung Hsing University Taichung 402202 Taiwan Graduate Institute of Chinese Medical Science China Medical University Taichung 406040 Taiwan Department of Applied Mathematics Feng Chia University Taichung 407102 Taiwan Institute of Genomics and Bioinformatics National Chung Hsing University Taichung 402202 Taiwan School of Biomedical Sciences Faculty of Biological Sciences and the Astbury Centre for Structural Molecular Biology University of Leeds Leeds LS2 9JT United Kingdom Department of Life Science Tunghai University Taichung 407224 Taiwan Institute of Biochemical Sciences National Taiwan University Taipei 106319 Taiwan Ph.D Program in Translational Medicine National Chung Hsing University Taichung 402202 Taiwan

The K+ uptake system KtrAB is essential for bacterial survival in low K+ environments. The activity of KtrAB is regulated by nucleotides and Na+. Previous studies proposed a putative gating mechanism of KtrB regulated...

The K⁺ uptake system KtrAB is essential for bacterial survival in low K⁺ environments. The activity of KtrAB is regulated by nucleotides and Na⁺. Previous studies proposed a putative gating mechanism of KtrB regulated by KtrA upon binding to ATP or ADP. However, how Na⁺ activates KtrAB and the Na⁺ binding site remain unknown. Here we present the cryo-EM structures of ATP- and ADP-bound KtrAB from Bacillus subtilis (BsKtrAB) both solved at 2.8 Å. A cryo-EM density at the intra-dimer interface of ATP-KtrA was identified as Na⁺, as supported by X-ray crystallography and ICP-MS. Thermostability assays and functional studies demonstrated that Na⁺ binding stabilizes the ATP-bound BsKtrAB complex and enhances its K⁺ flux activity. Comparing ATP- and ADP-BsKtrAB structures suggests that BsKtrB Arg417 and Phe91 serve as a channel gate. The synergism of ATP and Na⁺ in activating BsKtrAB is likely applicable to Na⁺-activated K⁺ channels in central nervous system. © The Author(s) 2024.

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