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Effect of cigarette smoke extract on lipopolysaccharide-activated mitogen-activated protein kinase signal transduction pathway in cultured cells

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Chinese Medical Journal 2007年第12期120卷 1075-1081页

作者： LI Wen XU Yong-jian SHEN Hua-hao Department of Respiratory Medicine Second Affiliated Hospital College of Medicine and Institute of Respiratory Diseases Zhejiang University Hangzhou 310009 China Department of Respiratory Medicine Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China

Background Lipopolysaccharide （LPS） forms outer membrane of the wall of Gram-negative cells. LPS can directly cause damage to epithelia of respiratory tract and is the major factor responsible for the chronic inflammation of respiratory passage. The mitogen-activated protein kinase （MAPK） signal transduction pathway of the airway epithelia is intimately associated with the action of LPS. The chronic inflammation of respiratory tract and smoking are interrelated and entwined in the development and progression of chronic lung diseases. This study was designed to examine the effects of cigarette smoke extract （CSE） and LPS on MAPK signal transduction pathway in order to further understand the roles CSE and LPS play in chronic lung inflammation. Methods Cultured primary human epithelial cells of airway were divided into four groups according to the stimulants used： blank control group, LPS-stimulation group, CSE-stimulation group and CSE plus LPS group. Western blotting was employed for the detection of phosphorylation level of extracellular-signal-regulated-kinase （ERK1/2）, p38 MAPK and c-Jun N-terminal kinase （JNK）. The expression of cytokines of MAPK transduction pathway （granulocyte-macrophage colony stimulating factor （GM-CSF） and mRNA of IL-8） in the primary epithelial cells of respiratory tract was also determined. Results Western blotting revealed that the phosphorylation levels of ERK1/2, p38 MAPK and JNK were low and 2 hours after the LPS stimulation, the phosphorylation of ERK1/2, p38 MAPK and JNK were all increased. There was a significant difference in the phosphorylation between the LPS-stimulation group and blank control group （P〈0.05）; no significant difference was found between CSE-stimulation group and blank control group （P〉0.05）; there was a significant difference between CSE ＋ LPS group and blank control group and between CSE ＋ LPS group and LPS group （P〈0.05）. The phosphorylation of CSE-LPS group was higher than that of blank control group but lower than that of LPS group. In blank control g

关键词： smoking lipopolysaccharide mitogen-activated protein kinase signal transduction pathway interleukin-8 epithelial cells granulocyte-macrophage colony stimulating factor

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Role of Toll-like receptor 4 and Janus kinase and signal transducer and activator of transcription signal transduction pathway in sepsis-induced brain damage

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Neural Regeneration Research 2011年第32期6卷 2511-2515页

作者： Haiyan Yin Jianrui Wei Rui Zhang Xiaoling Ye Youfeng Zhu ICU Department Guangzhou Red Cross Hospital Affiliated to Medical College of Jinan University Guangzhou 510220 Guangdong ProvinceChina Department of Cardiology Guangzhou Red Cross Hospital Affiliated to Medical College of Jinan University Guangzhou 510220 GuangdongProvince China

The Janus kinase and signal transducer and activator of transcription （JAK/STAT） signal transduction pathway is involved in sepsis-induced functional damage to the heart, liver, kidney, and other organs. However, the cellular and molecular mechanisms underlying sepsis-induced brain damage remain elusive. In the present study, we found severe loss of neurons in the hippocampal CA1 region in rats with sepsis-induced brain damage following intraperitoneal injection of endotoxin, The expression of toll-like receptor 4, tumor necrosis factor a, and interleukin-6 was significantly increased in brain tissues following lipopolysaccharide exposure. AG490 （JAK2 antagonist） and rapamycin （STAT3 antagonist） significantly reduced neuronal loss and suppressed the increased expression of toll-like receptor 4, tumor necrosis factor a, and interleukin-6 in the hippocampal CA1 region in sepsis-induced brain damaged rats. Overall, these data suggest that blockade of the JAK/STAT signal transduction pathway is neuroprotective in sepsis-induced brain damage via the inhibition of toll-like receptor 4, tumor necrosis factor a, and interleukin-6 exoression.

关键词： brain damage Janus kinase and signal transducer and activator of transcription sepsis signal transduction pathway Toll-like receptor 4

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YWHAH activates the HMGA1/PI3K/AKT/mTOR signaling pathway by positively regulating Fra-1 to affect the proliferation of gastric cancer cells

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Oncology Research 2023年第4期31卷 615-630页

作者： JUNYU HE FENG ZENG XI JIN LIN LIANG MENGXIANG GAO WENTAO LI GUIYUAN LI YANHONG ZHOU NHC Key Laboratory of Carcinogenesis Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha410013China Cancer Research Institute Basic School of MedicineCentral South UniversityChangsha410078China Hunan Key Laboratory of Cancer Metabolism Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha410013China

Fos-related antigen 1(Fra-1)is a nuclear transcription factor that regulates cell growth,differentiation,and apoptosis.It is involved in the proliferation,invasion,apoptosis and epithelial mesenchymal transformation of malignant tumor cells.Fra-1 is highly expressed in gastric cancer(GC),affects the cycle distribution and apoptosis of GC cells,and participates in GC occurrence and development.However,the detailed mechanism of Fra-1 in GC is unclear,such as the identification of Fra-1-interacting proteins and their role in GC pathogenesis.In this study,we identified tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta(YWHAH)as a Fra-1-interacting protein in GC cells using co-immunoprecipitation combined with liquid chromatography-tandem mass spectrometry.Experiments showed that YWHAH positively regulated Fra-1 mRNA and protein expression,and affected GC cell proliferation.Whole proteome analysis showed that Fra-1 affected the activity of the high mobility group AT-hook 1(HMGA1)/phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K)/protein kinase B(AKT)/mechanistic target of rapamycin(mTOR)signaling pathway in GC cells.Western blotting and flow cytometry confirmed that YWHAH activated HMGA1/PI3K/AKT/mTOR signaling pathway by positively regulating Fra-1 to affect GC cell proliferation.These results will help to discover new molecular targets for the early diagnosis,treatment,and prognosis prediction of GC.

关键词： Gastric cancer Fra-1 YWHAH signal transduction pathway Cell proliferation

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Regulatory Mechanisms of the Molecular pathways in Fibrosis Induced by MicroRNAs

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Chinese Medical Journal 2016年第19期129卷 2365-2372页

作者： Cui Yang Si-Dao Zheng Hong-Jin Wu Shao-Jun Chen Department of Cardiology Huairou Hospital of Traditional Chinese Medicine Beijing 101400 China Department of Cardiology Beijing Hospital of Integrated Traditional Chinese and Western Medicine Beijing 100039 China Department of Cardiology Beijing Haidian Hospital Haidian Section of Peking University Third Hospital Beijing 100191 China

Objective：MicroRNAs （miRNAs or miRs） play critical roles in the fibrotic process in different organs.We summarized the latest research progress on the roles and mechanisms of miRNAs in the regulation of the molecular signaling pathways involved in fibrosis.Data Sources：Papers published in English from January 2010 to August 2015 were selected from the PubMed and Web of Science databases using the search terms ＂microRNA＂,＂miR＂,＂transforming growth factor β＂,＂tgf β＂,＂mitogen-activated protein kinase＂,＂mapk＂,＂integrin＂,＂p38＂,＂c-Jun NH2-terminal kinase＂,＂jnk＂,＂extracellular signal-regulated kinase＂,＂erk＂,and ＂fibrosis＂.Study Selection：Articles were obtained and reviewed to analyze the regulatory effects of miRNAs on molecular signaling pathways involved in the fibrosis.Results：Recent evidence has shown that miRNAs are involved in regulating fibrosis by targeting different substrates in the molecular processes that drive fibrosis,such as immune cell sensitization,effector cell activation,and extracellular matrix remodeling.Moreover,several important molecular signaling pathways involve in fibrosis,such as the transforming growth factor-beta （TGF-β） pathway,mitogen-activated protein kinase （MAPK） pathways,and the integrin pathway are regulated by miRNAs.Third,regulation of the fibrotic pathways induced by miRNAs is found in many other tissues in addition to the heart,lung,liver,and kidney.Interestingly,the actions of many drugs on the human body are also induced by miRNAs.It is encouraging that the fibrotic process can be blocked or reversed by targeting specific miRNAs and their signaling pathways,thereby protecting the structures and functions of different organs.Conclusions：miRNAs not only regulate molecular signaling pathways in fibrosis but also serve as potential targets of novel therapeutic interventions for fibrosing diseases.

关键词： Fibrosis Integrins MicroRNAs Mitogen-activated Protein Kinases signal transduction pathway Transforming Growth Factor-beta

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Functional Insights of Plant GSK3-like Kinases： Multi-Taskers in Diverse Cellular signal transduction pathways

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Molecular Plant 2015年第4期8卷 552-565页

作者： Ji-Hyun Youn Tae-Wuk Kim Department of Life Science College of Natural Sciences Hanyang University Seou1133-791 Korea Naturat Science Institute Hanyang University Seou1133-791 Korea

The physiological importance of GSK3-like kinases in plants emerged when the functional role of plant GSK3-like kinases represented by BIN2 was first elucidated in the brassinosteroid （BR）-regulated signal transduction pathway. While early studies focused more on understanding how GSK3-like kinases regulate BR signaling, recent studies have implicated many novel substrates of GSK3-like kinases that are involved in a variety of cellular processes as well as BR signaling. Plant GSK3-like kinases play diverse roles in physiological and developmental processes such as cell growth, root and stomatal cell development, flower development, xylem differentiation, light response, and stress responses. Here, we review the progress made in recent years in understanding the versatile functions of plant GSK3-like kinases. Based on the relationship between GSK3-like kinases and their newly identified substrates, we discuss the physiological and biochemical relevance of various cellular signaling mediated by GSK3-like kinases in plants.

关键词： GSK3-like kinases brassinosteroids signal transduction pathway Arabidopsis rice

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Blockage of PI3K/PKB/P27^(kip1) signaling pathway can antagonize 17β-estradiol-induced Ishikawa proliferation and cell cycle progression

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Chinese Medical Journal 2006年第3期119卷 242-245页

作者： GUO Rui-xia WEI Li-hui QIAO Yu-huan WANG Jian-liu TANG Jian-min Department of Gynecology People＇s Hospital Peking UniversityBeijing 100044 China Department of Obstetrics and Gynecology First Teaching HospitalZhengzhou University Zhengzhou 450052 China Department of Internal Medicine People＇s Hospital PekingUniversity Beijing 100044 China

It is well-known that risk for endometrial adenocarcinoma increases in patients with high level ofestrogen that is unopposed by progestin. And activation of extracellular signal-regulated kinase （ERK） and phosphatidylinositol 3 kinase/protein kinase B （PI3K/PKB） pathway are responsible for hormone-dependent cell growth in endometrial carcinoma. PI3K produces phosphatidylinositol- 3-phosphates by phosphory-lating the D3 hydroxyl of phosphoinositides, leading to membrane translocation of PKB,

关键词： endometrial neoplasms estrogens signal transduction pathway cell cycle cell proliferation

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Antioxidant mechanism of tea polyphenols and its impact on health benefits

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Animal Nutrition 2020年第2期6卷 115-123页

作者： Zhaoming Yan Yinzhao Zhong Yehui Duan Qinghua Chen Fengna Li College of Animal Science and Technology Hunan Agricultural UniversityChangsha 410128China Laboratory of Animal Nutritional Physiology and Metabolic Process Institute of Subtropical Agriculture Chinese Academy of SciencesKey Laboratory of Agro-ecological Processes in Subtropical RegionHunan Provincial Engineering Research Center for Healthy Livestock and Poultry ProductionScientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-CentralMinistry of AgricultureChangsha 410125China College of Animal Science South China Agricultural UniversityGuangzhou 510642China Hunan Co-Innovation Center of Animal Production Safety Hunan Collaborative Innovation Center for Utilization of Botanical Functional IngredientsChangsha 410128China

Tea trees have a long history of cultivation and utilization.People in many countries have the habit of drinking tea and choosing green tea,oolong tea,or black tea according to different regions and personal tastes.Tea polyphe nols are a general term for polyphenol co mpounds in tea,and has been shown to have good effects on antioxidant,anti-inflammatory,cancer prevention and regulation of lipid metabolism.Tea polyphenols have been widely used as antioxidants in disease treatment and animal husbandry,but their specific mechanism of action needs to be further clarified and revealed.This review focuses on the definition,classification,antioxidant activity and the regulation of signaling pathways of tea polyphenols.This paper also aims to examine the application of tea polyphenols in human and animal health,providing a scientific basis for this application in addition to proposing future directions for the development of this resource.

关键词： Tea polyphenols Antioxidant activities Animal production signal transduction pathway

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Effects of Shikonin on the Proliferation and Activation of T Lymphocytes

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World Journal of Traditional Chinese Medicine 2018年第3期4卷 121-126页

作者： Xin Liu Jing?Xia Zhao Yan Wang Ping Li Beijing Hospital of Traditional Chinese Medicine Capital Medical University Beijing Institute of Traditional Chinese Medicine Beijing Key Laboratory of Clinic and Basic Research with TCM on Psoriasis

Objective: To investigate the effects of Chinese herbal monomer shikonin which has the function of cooling blood and detoxification on abnormally activated T lymphocyte and its related signal pathways and to elucidate the role of shikonin in the pathological state of psoriasis and its mechanism of treating psoriasis. Materials and Methods: Jurkat E6?1 T lymphocytes were activated with phorbol ester and ionomycin. The shikonin concentration of 0.5–2 μg/mL was applied to the cells, and the proliferation of T lymphocytes was detected by Cell Counting Kit?8 assay. Flow cytometry was used to measure CD69 expression on the cell membrane and intracellular free calcium ion concentration([Ca^(2+)]i); enzyme?linked immunosorbent assay was used to detect the levels of interleukin(IL)?2, interferon?γ(IFN?γ), and(TNF?α) released by activated T lymphocytes; quantitative polymerase chain reaction and Western blot were used to observe the expression of nuclear transcription factor m RNA and protein, respectively. Results: Different concentrations of shikonin could significantly inhibit cell proliferation, CD69 expression, and secretion of Th1 cytokines. In addition, shikonin could effectively reduce the [Ca^(2+)]i and protein kinase C phosphorylation proteins. Besides that, shikonin could significantly reduce the nuclear transcription factor nuclear factor of activated T lymphocytes mRNA expression, downregulate c?Jun mRNA and protein expression, and inhibit NF?κB protein expression. All the above indicators show a certain dose–effect relationship. Conclusions: Shikonin can exert immune regulation by inhibiting the function of overactivated T lymphocytes. Hence, this study provides experimental basis for the mechanism and application prospect of shikonin in the treatment of psoriasis.

关键词： psoriasis shikonin signal transduction pathway Tlymphocyte activation treatment principle of cooling blood and detoxification

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TGF-β1/SMAD signalING pathway MEDIATES p53-DEPENDENT APOPTOSIS IN HEPATOMA CELL LINES

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Chinese Medical Sciences Journal 2006年第1期21卷 33-35页

作者： Chun-lei Wang Yuan-lian Wan Yu-cun Liu Zhi-qiang Huang Department of General Surgery the First Hospital Peking University Beijing 100034 Institute of Hepatobiliary Surgery General Hospital of People＇s Liberation Army Beijing 100853

Objective To determine whether transforming growth factor betal (TGF-β1)/Smad signaling pathway mediates p53-dependent apoptosis in hepatoma cell lines.Methods Three human hepatic carcinoma cell lines, HepG2, Huh-7, and Hep3B, were used in this study.TGF-β1-induced apoptosis in hepatic carcinoma cell lines was analyzed using TUNEL assay.For identifying the mechanism of apoptosis induced by TGF-β1, cell lines were transfected with a TGF-β1-inducible luciferase reportor plasmid containing Smad4 binding elements.After transfection, cells were treated with TGF-β1, then assayed for luciferase activity.Results The apoptosis rate of HepG2 cell lines (48.51%± 8.21%) was significantly higher than control ( 12.72%±2.18%, Psignaling transdution pathway.TGF-β1/Smad signaling pathway might mediate p53-dependent apoptosis in hepatoma cell lines.

关键词： transforming growth factor-β1 apoptosis hepatoma cell line signal transduction pathway

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Bitter components related to alleviating intestinal obstruction in traditional Mongolian medicine

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TMR Theory and Hypothesis 2020年第2期3卷 337-347页

作者： Hong-Zhen Yu Li-Sha A Xiao-Ping Ji Sung-Bo Cho Gen-Na Ba Peng-Fei Han Ming-Hai Fu School of Mongolian Medicine Inner Mongolia University for NationalitiesTongliaoChina Faculty of Psychology Southwest UniversityChongqingChina.

Intestinal obstruction is a blockage that keeps digesta from passing through upper or lower intestine.Traditional Mongolian medicine(TMM)has been proven to be efficacious in the clinical treatment of intestinal obstruction.However,the mechanism of its treatment has not been studied.The bitter taste receptors(T2Rs)are highly expressed in the extra-oral digestive system,such as gastrointestinal tract,which can regulate gastrointestinal peristalsis and contraction of gastrointestinal smooth muscle.In the respiratory system,T2Rs can relax the airway smooth muscle and effectively alleviate asthma symptoms.In this review,the theory and clinical applications of bitter herbs in TMM were discussed and the functional expression of T2Rs and bitter taste signal transduction pathway were analyzed to investigate whether bitter Mongolian medicine may play an effective role in promoting gastrointestinal peristalsis.Therefore,the scientific connotation of the theory of bitter medicinal property of TMM was interpreted by combining T2Rs research and application of modern technology.This new research approach may enrich and improve the basic theory and accelerate the modernization of TMM.

关键词： Intestinal obstruction Mongolian medicine Bitter taste receptors signal transduction pathway

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