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Na^(+)/K^(+)-ATPase:ion pump,signal transducer,or cytoprotective protein,and novel biological functions

Neural Regeneration Research 2024年第12期19卷 2684-2697页

作者： Songqiang Huang Wanting Dong Xiaoqian Lin jinsong bian Department of Pharmacology Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and DiseasesSchool of MedicineSouthern University of Science and TechnologyShenzhenGuangdong ProvinceChina Department of Pharmacology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into cells.Additionally,Na^(+)/K^(+)-ATPase participates in Ca^(2+)-signaling transduction and neurotransmitter release by coordinating the ion concentration gradient across the cell membrane.Na^(+)/K^(+)-ATPase works synergistically with multiple ion channels in the cell membrane to form a dynamic network of ion homeostatic regulation and affects cellular communication by regulating chemical signals and the ion balance among different types of cells.Therefo re,it is not surprising that Na^(+)/K^(+)-ATPase dysfunction has emerged as a risk factor for a variety of neurological diseases.However,published studies have so far only elucidated the important roles of Na^(+)/K^(+)-ATPase dysfunction in disease development,and we are lacking detailed mechanisms to clarify how Na^(+)/K^(+)-ATPase affects cell function.Our recent studies revealed that membrane loss of Na^(+)/K^(+)-ATPase is a key mechanism in many neurological disorders,particularly stroke and Parkinson's disease.Stabilization of plasma membrane Na^(+)/K^(+)-ATPase with an antibody is a novel strategy to treat these diseases.For this reason,Na^(+)/K^(+)-ATPase acts not only as a simple ion pump but also as a sensor/regulator or cytoprotective protein,participating in signal transduction such as neuronal autophagy and apoptosis,and glial cell migration.Thus,the present review attempts to summarize the novel biological functions of Na^(+)/K^(+)-ATPase and Na^(+)/K^(+)-ATPase-related pathogenesis.The potential for novel strategies to treat Na^(+)/K^(+)-ATPase-related brain diseases will also be discussed.

关键词： antibody biological functions cellular communication electrochemical gradient ion balance ion channels Na^(+)/K^(+)-ATPase neurological diseases neurotransmitter release signal transduction

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Therapeutic potential of gasotransmitters for cold stress-related cardiovascular disease

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Frigid Zone Medicine 2022年第1期2卷 10-24页

作者： Haijian Sun Xiaowei Nie Kangying Yu jinsong bian School of Traditional Chinese Pharmacy China Pharmaceutical UniversityNanjing 211198China Shenzhen Key Laboratory of Respiratory Diseases Shenzhen People’s Hospital(The First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518055China Nursing School of Wuxi Taihu University Wuxi 214064China Department of Pharmacology School of MedicineSouthern University of Science and TechnologyShenzhen 518055China National University of Singapore(Suzhou)Research Institute Suzhou 215000China

Growing evidence has shown that exposure to low ambient temperature poses a huge challenge to human health globally.Actually,cold stress is closely associated with a higher incidence of cardiovascular morbidity and mortality in winter or in cold regions.Cellular and molecular mechanisms underlying cardiovascular complications in response to cold exposure have yet to be fully clarified.Considering that cold exposure is an important risk of cardiovascular complications,it is necessary to clarify the molecular mechanism of cold stress-induced cardiovascular diseases and to develop effective intervention strategies.Hydrogen sulfide(H2S),nitric oxide(NO),and carbon monoxide(CO)are well-known gasotransmitters that are endogenously produced in many biological systems.Accumulating studies have demonstrated that these gasotransmitters play a critical role in a wide spectrum of physiological and/or pathophysiological processes by regulating numerous signaling pathways.These gas signal molecules are emerging as important players in cardiovascular homeostasis,and disruption of these gasotransmitters is critically implicated in cardiovascular anomalies,such as hypertension,atherosclerosis,myocardial ischemia,heart failure,and stroke.Also,evidence is emerging that H2S,NO,and CO may be involved in the pathologies of cold stress-induced cardiovascular ailments.In this review,we aim to highlight and discuss the recent advances towards the development of gasotransmitters-based therapeutics for cold stress-related cardiovascular pathogenesis.We believe that the effects of H2S,NO,and CO on cardiovascular regulation under cold environment will attract tremendous interest in the near future as they serve as novel regulators of cardiovascular biology in cold environment.

关键词： cold stress cardiovascular diseases hydrogen sulfide nitric oxide carbon monoxide

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APOBEC3B and IL-6 form a positive feedback loop in hepatocellular carcinoma cells

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Science China(Life Sciences) 2017年第6期60卷 617-626页

作者： Shuran Li Xueyang Bao Duowei Wang Linjun You Xianjing Li Hongbao Yang jinsong bian Yun Wang Yong Yang State Key Laboratory of Natural Medicines Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease Center for New Drug Safety Evaluation and Research China Pharmaceutical University Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore

APOBEC3 protein families, a DNA cytidine deaminase, were up-regulated in multiple tumors. However, the relationship between Hepatocellular carcinoma(HCC) and APOBEC3B(A3B) remains unknown. It has been confirmed that interleukin-6(IL-6)has significant impacts on oncogenesis of HCC. Here, we reported that the expression of IL-6 was substantially up-regulated by A3 B in HepG2 cells. A3 B induced IL-6 expression through relocating HuR to enhance the IL-6 mRNA stability. Further analysis indicated that IL-6 also increased the expression of A3 B through JAK1/STAT3 signaling pathway, which formed a positive feedback to maintain the continuous expression of A3 B and IL-6, and thereby promoted the prolonged non-resolving inflammation. Collectively, these findings suggest that A3 B is essential for oncogenesis of HCC, and is a potential target for preventive intervention.

关键词： IL-6 肝细胞癌反馈回路白细胞介素-6 胞嘧啶脱氨酶 mRNA 信号通路 DNA

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Arthroscopic Minimally Invasive Surgery for Knee Joint Gouty Arthritis

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Journal of Clinical and Nursing Research 2019年第5期3卷 19-22页

作者： Yi Fan Cheng Zhang Guotao Zheng Shuai Wu Yujie Wang jinsong bian Department of Orthopedics Cangzhou People’s HospitalCangzhouHebei061000China

Objective:To analyse the efficacy of arthroscopic minimally invasive surgery in patients with knee joint gouty arthritis.Methods:A retrospective analysis method was carried out on randomly selected 56 patients with knee gouty arthritis from early July 2018 to the end of June 2019.All patients underwent arthroscopic minimally invasive surgery.Results:In this study,the patients were followed for 10 months.The Lysholm score of knee function was found to be significantly higher after treatment compared to the scores before treatment(P<0.05).Conclusion:Arthroscopic minimally invasive surgery is a promising method to treat for knee joint gouty arthritis.

关键词： Arthroscopy minimally invasive surgery Knee joint gouty arthritis Effect

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All in the timing： comparison of cardioprotection induced by H2S preconditioning and post-infarction treatment

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中国药理通讯 2009年第2期26卷 5-5页

作者： jinsong bian Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore

Hydrogen sulfide (H2S) is a novel gasotransmitter alongside nitric oxide and carbon monoxide. We recently found that hydrogen sulfide regulates heart contractile function via changing intracellular calcium, pH and cAMP level. Both pre- and post-conditioning with H2S produce significant cardioprotection against ischemia insults via activation of ATP-sensitive K+ channels, protein kinase C, mitogen-activated protein kinases, PI3K/Akt and cycloxygenase-2/prostaglandin E2 pathways. These findings provide evidence that H2S may protect heart in both physiological and pathological situations.

关键词：心脏治疗方法硫化氢蛋白激酶

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A Shape-Memory Deployable Subsystem with a Large Folding Ratio in China’s Tianwen-1 Mars Exploration Mission

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Engineering 2023年第9期28卷 49-57页

作者： Chengjun Zeng Liwu Liu Yang Du Miao Yu Xiaozhou Xin Tianzhen Liu Peilei Xu Yu Yan Dou Zhang Wenxu Dai Xin Lan Fenghua Zhang Linlin Wang Xue Wan Wenfeng bian Yanju Liu jinsong Leng Department of Astronautical Science and Mechanics Harbin Institute of TechnologyHarbin 150001China Shanghai Institute of Satellite Engineering Shanghai 201109China Center for Composite Materials and Structures Harbin Institute of TechnologyHarbin 150080China Department of Civil Engineering Harbin Institute of TechnologyWeihai 264209China

Once China’s Tianwen-1 Mars probe arrived in a Mars orbit after a seven-month flight in the deep cold space environment,it would be urgently necessary to monitor its state and the surrounding environment.To address this issue,we developed a flexible deployable subsystem based on shape memory polymer composites(SMPC-FDS)with a large folding ratio,which incorporates a camera and two temperature telemetry points for monitoring the local state of the Mars orbiter and the deep space environment.Here,we report on the development,testing,and successful application of the SMPC-FDS.Before reaching its Mars remote-sensing orbit,the SMPC-FDS is designed to be in a folded state with high stiffness;after reaching orbit,it is in a deployed state with a large envelope.The transition from the folded state to the deployed state is achieved by electrically heating the shape memory polymer composites(SMPCs);during this process,the camera on the SMPC-FDS can capture the local state of the orbiter from multiple angles.Moreover,temperature telemetry points on the SMPC-FDS provide feedback on the environment temperature and the temperature change of the SMPCs during the energization process.By simulating a Mars on-orbit space environment,the engineering reliability of the SMPC-FDS was comprehensively verified in terms of the material properties,structural dynamic performance,and thermal vacuum deployment feasibility.Since the launch of Tianwen-1 on 23 July 2020,scientific data on the temperature environment around Tianwen-1 has been successfully acquired from the telemetry points on the SMPCFDS,and the local state of the orbiter has been photographed in orbit,showing the national flag of China fixed on the orbiter.

关键词： Flexible deployable structure Shape memory polymer composite Mars exploration Temperature telemetry On-orbit deployment

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Preliminary design and analysis of a cubic deployable support structure based on shape memory polymer composite

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International Journal of Smart and Nano Materials 2016年第2期7卷 106-118页

作者： Fengfeng Li Liwu Liu Xin Lan Xiaojun Zhou Wenfeng bian Yanju Liu jinsong Leng Department of Astronautical Science and Mechanics Harbin Institute of Technology(HIT)HarbinPeople’s Republic of China Centre for Composite Materials Science Park of Harbin Institute of Technology(HIT)HarbinPeople’s Republic of China Department of Civil Engineering Harbin Institute of TechnologyWeihaiChina

The deployable structures based on shape memory polymer com-posites(SMPCs)have been developed for its unique properties,such as high reliability,low-cost,lightweight,and self-deployment without complex mechanical devices compared with traditional deployable structures.In order to increase the inflatable structure system’s robustness and light the weight of it,a cubic deployable support structure based on SMPC is designed and analyzed pre-liminarily.The cubic deployable support structure based on SMPC consists of four dependent spatial cages,each spatial cage is composed of 12 three-longeron SMPC truss booms and end con-nections.The shape recovery of arc-shaped deployable laminates drive the three-longeron SMPC truss booms to unfold,thus realize the expansion of the deployable support structure.The concept and operation of the cubic deployable support structure are described in detail.A series of experiments are performed on the three-longeron deployable laminates unit and the simplified cubic deployable support structure to investigate the shape recovery behavior in the deployment process.Results indicate that the cubic deployable support structure has a high deployment-tgo-stowage volume ratio and can achieve self-deployment,package,and deploy without complex mechanical devices.

关键词： Shape memory polymer composites deployable structure shape recovery experiment

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Na+/K+-ATPase is a novel target to treat anxiety

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中国药理学与毒理学杂志 2023年第7期37卷 541-541页

作者： HUANG Songqiang NIE Xiaowei bian jinsong Department of Pharmacology School of MedicineSouthern University of Science and Technology Shenzhen Key Laboratory of Respiratory Diseases Shenzhen People's Hospital

OBJECTIVE Na+/K+-ATPase (NKA) is a large membrane protein expressed universally in all cells.It is indispensable for the maintenance of ionic gradient.We previously reported that the dysfunction of this pump in neurons and astrocytes contributes to stroke and neurodegenerative diseases,respectively.However,its roles in the microglia and stress-related diseases are still unclear.METHODS Two classical models,chronic restraint stress (CRS) model and electronic foot shock(ES) model,were used to study the pathogenesis of anxiety in either NKAα1 global knockout (NKAα1 GKO) mice or NKAα1 conditional knockout (NKAα1 CKO) mice.Behavioral tests like open-field test,elevated plus maze,Morris water maze,novel object recognition test and gait imaging test were performed.A variety of molecular biological methods were employed,including RNA sequencing (RNA-seq) analyses,immunofluorescence and electrophysiological recordings etc.RESULTS NKAα1 deficiency had a broad impact on physical stress-induced anxiety-like behavior,but failed to exacerbate CRS induced memory deficits.Electrophysiology experiment showed that NKAα1 GKO and NKAα1 CKO mice exhibited neuronal hyperexcitability under chronic stress.The underlying mechanisms may involve neuroinflammation,as NKAα1 deficiency exacerbated stress-induced microglia activation in vivo.Similarly,inhibition or downregulation of NKA α 1 aggravated LPS+ATP-induced inflammation in vitro.DR5-12D,a monoclonal antibody against the DR-region of NKAa1,improved stress-induced anxietylike behavior through amelioration of the neuronal hyperexcitability and neurogenesis deficit in the ventral hippocampus of mice.CONCLUSION NKA is closely related to neuroinflammation in microglia and DR-region of NKA a1 subunit may serve as a novel target to treat stressinduced anxiety.

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Activation of Na^＋/K^＋ ATPase with DR Region Antibody Produces Cardioprotection

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中国药理通讯 2013年第3期30卷 10-11页

作者： Fei Hua Jin Zheng jinsong bian Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore Singapore

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途径工程改造谷氨酸棒杆菌合成L-半胱氨酸

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食品与发酵工业 2022年第20期48卷 22-28页

作者：卞金玉张晓梅徐国强史劲松许正宏江南大学药学院江苏无锡214122 粮食与发酵国家工程实验室(江南大学) 江苏无锡214122

L-半胱氨酸是一种重要的含硫氨基酸,广泛应用在医药、食品和化妆品等行业。该文以实验室保藏的一株高产L-丝氨酸的谷氨酸棒杆菌(Corynebacterium glutamicum)A36为出发菌株,通过加强表达丝氨酸O-乙酰基转移酶(serine O-acetyltransferas... 详细信息

L-半胱氨酸是一种重要的含硫氨基酸,广泛应用在医药、食品和化妆品等行业。该文以实验室保藏的一株高产L-丝氨酸的谷氨酸棒杆菌(Corynebacterium glutamicum)A36为出发菌株,通过加强表达丝氨酸O-乙酰基转移酶(serine O-acetyltransferase,SAT)、O-乙酰基-L-丝氨酸巯基化酶-A和转运蛋白Bcr编码基因强化L-半胱氨酸合成和转运,敲除L-半胱氨酸降解途径关键酶弱化其降解,构建系列重组菌株,其中重组菌S-C-7的L-半胱氨酸产量最高,为286.7 mg/L。进一步通过优化硫源提高菌株S-C-7的L-半胱氨酸产量,结果表明,最佳硫源为硫代硫酸钠,当发酵24 h时添加12 g/L硫代硫酸钠,L-半胱氨酸的产量最高,为581.6 mg/L,较优化前提高1.0倍。最后,在5 L发酵罐对S-C-7进行发酵评价,L-半胱氨酸产量达到1.2 g/L,是目前文献报道谷氨酸棒杆菌产L-半胱氨酸的最高产量;为实现谷氨酸棒杆菌发酵生产L-半胱氨酸奠定了基础。

关键词： L-半胱氨酸谷氨酸棒杆菌合成途径降解途径转运蛋白

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