進階搜尋


   電子論文尚未授權公開,紙本請查館藏目錄
(※如查詢不到或館藏狀況顯示「閉架不公開」,表示該本論文不在書庫,無法取用。)
系統識別號 U0026-2708201201251700
論文名稱(中文) 超細碳黑微粒暴露引發肺上皮細胞和血管損傷的分子機制探討
論文名稱(英文) Molecular mechanisms of ultrafine carbon black particle-induced pulmonary epithelial and vascular injury
校院名稱 成功大學
系所名稱(中) 環境醫學研究所
系所名稱(英) Institute of Environmental and Occupational Health
學年度 100
學期 2
出版年 101
研究生(中文) 邱嘉貞
研究生(英文) Jia-Jhen Chiu
學號 s76981050
學位類別 碩士
語文別 中文
論文頁數 66頁
口試委員 口試委員-劉明毅
口試委員-蔡美玲
指導教授-張志欽
中文關鍵字 超細碳黑微粒  一維電泳串聯質譜儀  肺部損傷 
英文關鍵字 ultrafine carbon black  1-D geLC/MS/MS  lung injury 
學科別分類
中文摘要 蛋白質體學的研究方法可以偵測蛋白質的變化增進我們了解肺部損傷的機制,我們先前蛋白質體學研究發現超細碳黑微粒(ultrafine carbon black,ufCB)暴露後會破壞上皮細胞造成EGFR和LIFR釋放至肺泡沖堤液使表現量增加,動物和細胞實驗中也證實超細碳黑微粒誘發肝細胞生長因子活化ERK1/2促使上皮細胞增生,儘管如此,目前對於超細碳黑微粒造成肺部傷害的機制仍有待探索,因此本篇研究的目的為調查和鑑定超細碳黑微粒誘發肺部損傷蛋白質的表現。動物實驗分別以超細碳黑微粒(200μg/mouse)和PBS暴露ICR公鼠24小時,利用二甲基標示法結合1-D geLC/MS/MS分析其肺部組織蛋白質的表現。結果顯示共計鑑定出115個蛋白質,其中包含9個訊號傳遞及9個細胞膜蛋白質,我們進一步以西方墨點法驗證了14-3-3 zeta、Rho GDIα (Rho GDP dissociation inhibitor alpha)和ICAM-1(intercellular adhesion molecule 1)蛋白質的表現量,並提出新的研究假說,(1)超細碳黑微粒暴露造成肺部上皮細胞14-3-3蛋白質表現異常,阻斷細胞凋亡反應;(2)暴露超細碳黑微粒經由活化血管的升壓激素受體AT1R,促進Rho GDIα表現及Rho A/ROCK活性增加,進而影響血管收縮反應。由肺泡上皮第二型細胞株(L2)實驗發現14-3-3 zeta可被超細碳黑微粒誘發表現增加,但14-3-3 sigma和BAD蛋白則下降,且呈劑量效應關係。此外,以WKY大鼠肺部動脈血管暴露超細碳黑微粒後顯示Rho GDIα和上游AT1R 的表現量會增加,且有劑量效應關係,同時亦發現不論是在肺組織或是肺動脈中細胞間黏附因子(ICAM-1)在超細碳黑微粒暴露後表現量明顯高於對照組,顯示超細碳黑微粒造成肺部和血管急性損傷。綜合以上結果,本篇研究利用1-D geLC/MS/MS分析方法,發現超細碳黑微粒暴露後因14-3-3蛋白質異常表現造成肺部上皮細胞走向抗凋亡反應,14-3-3 sigma降低顯示上皮細胞DNA受損並與癌症發展有關,此外,暴露超細碳黑微粒可能經由活化AT1R促進Rho GDIα表現和Rho A/ROCK造成血管收縮。未來必須進一步利用siRNA抑制確認14-3-3表現異常和細胞凋亡的關係,並釐清MYPT1活化與血管收縮反應的機制。
英文摘要 Lung proteome research has the potential to identify proteins that are responsible for the development of adverse pulmonary outcomes. Our previous study have demonstrated that acute exposure to ufCB caused epithelial shedding, with increased epidermal growth factor receptor (EGFR) and leukemia inhibitory factor receptor (LIFR) in BAL fluid by lung proteome study. In vivo and in vitro study also show that ufCB could activate HGF and induced lung type II epithelial cell proliferation. However, the mechanism of ufCB-induced lung injury remains to be explored. The purpose of this study is to identify and investigate proteins contributing to ufCB-induced pulmonary injury. In this study, ICR male mice were intratracheally instilled with ufCB at 200 (μg/mouse) for 24 hr. 1-D gel electrophoresis coupled with stable isotope dimethyl labeling and LC/MS/MS (1-D geLC/MS/MS dimethyl labeling) was applied to identify tissue proteins from lavaged lung that were associated with ufCB-induced pulmonary adverse outcomes. A total of 115 proteins were identified and quantified in ufCB-exposed lung tissue, including 9 signaling transduction and 9 membrane proteins. Western blotting verified that 14-3-3 zeta, Rho GDP dissociation inhibitor (GDI) alpha (Rho GDIα) and intercellular adhesion molecule 1(ICAM-1), were significantly increased in ufCB exposure group, compared with those in PBS group. We hypothesis that (1) ufCB exposure causes the dysregulation of 14-3-3 proteins, leading to apoptosis resistence. (2) ufCB exposure induces the upregulation Rho GDIα and activation of Rho A/ROCK via AT1R. The results show of that 14-3-3 zeta expression levels in the ufCB group were significantly more than those in the PBS group in L2 pulmonary epithelial cells. BAD and 14-3-3 sigma were significantly decrease after ufCB exposure. Experiments with lung pulmonary artery explants also showed that ufCB was capable of activity Rho GDIα and its upstream Angiotensin II type I receptor (AT1R). Moreover, the data demonstrated that ufCB caused the increase of sICAM-1 and MMPs activity in BALF after ufCB treatment. In conclusion, our study applies 1-D geLC/MS/MS dimethyl labeling and experimental studies to reveal a testable hypothesis that ultrafine particle exposure may cause aberrant expression of 14-3-3 proteins in pulmonary epithelial cells, leading to apoptosis resistance. The decrease of 14-3-3 sigma has been implicated in DNA damage and directly linked to tumor genesis. Moreover, exposure to ufCB may cause vascular constriction via AT1R activated Rho GDIα and Rho A/Rock signaling transduction. In the future, we need use the 14-3-3 siRNA to demonstrate ufCB exposure is capable of induceing apoptosis resistance in epithelial cells, and acivity MYPT1 to induce vascular constriction.
論文目次 中文摘要…………………………………………………………………… I
英文摘要…………………………………………………………………… III
致謝………………………………………………………………………… V
目錄………………………………………………………………………… VI
表目錄………………………………………………………………………VIII
圖目錄……………………………………………………………………… IX
第一章 序論
1.1前言………………………………………………………………………1
1.2研究目的…………………………………………………………………3
第二章 文獻探討
2.1超細微粒與健康效應 ………………………………………………… 4
2.2近代蛋白質體學之發展 ………………………………………………7
2.3蛋白質體學應用與微粒誘發肺部蛋白質改變 ………………………9
第三章 材料與方法
3.1材料 ………………………………………………………………12
3.2方法 ………………………………………………………………12
第四章 結果 …………………………………………………………………18
4.1超細碳黑微粒粒徑分佈(DLS)
4.2超細碳黑微粒造成肺損傷
4.2-1小鼠肺泡沖堤液中總細胞數
4.2-2小鼠肺泡沖堤液中巨噬細胞與嗜中性白血球數量比率
4.2-3小鼠肺泡沖堤液與肺組織總蛋白質表現量
4.3超細碳黑微粒與肺組織蛋白質改變
4.3-1暴露超細碳黑微粒肺部蛋白質與對照組之差異
4.3-2相關蛋白質D/H值
4.3-3肺部14-3-3 zeta、Rho GDIα和ICAM-1表現量
4.3-4實驗假說
4.4驗證假說
4.4-1超細碳黑微粒暴露造成14-3-3蛋白質表現異常,阻斷細胞凋亡反應
4.4-2超細碳黑微粒經由活化AT1R促進Rho GDIα表現及Rho A/ROCK
活性增加
第五章 討論…………………………………………………………………23
5.1暴露超細碳黑微粒會經由14-3-3 zeta調控肺泡上皮細胞抗凋亡反應
5.2超細碳黑微粒引起血管損傷機制
5.3超細碳黑微粒引起肺部損傷與發炎反應
第六章 結論…………………………………………………………………30
第七章 未來研究方向 ………………………………………………………31
第八章 參考文獻 ……………………………………………………………32
圖表 …………………………………………………………………………40
參考文獻 Li XY, Gilmour PS, Donaldson K, MacNee W. 1996. Free radical activity and pro-inflammatory effects of particulate air pollution (PM10) in vivo and in vitro. Thorax 51(12): 1216-1222.
Chang CC, Chiu HF, Wu YS, Li YC, Tsai ML, Shen CK, et al. 2005. The induction of vascular endothelial growth factor by ultrafine carbon black contributes to the increase of alveolar-capillary permeability. Environ Health Perspect 113(4): 454-460.
Chang CC, Chen SH, Ho SH, Yang CY, Wang HD, Tsai ML. 2007. Proteomic analysis of proteins from bronchoalveolar lavage fluid reveals the action mechanism of ultrafine carbon black-induced lung injury in mice. Proteomics 7(23): 4388-4397.
Ko FW, Tam W, Wong TW, Lai CK, Wong GW, Leung TF, et al. 2007a. Effects of air pollution on asthma hospitalization rates in different age groups in Hong Kong. Clin Exp Allergy 37(9): 1312-1319.
Etzel RA. 2003. How environmental exposures influence the development and exacerbation of asthma. Pediatrics 112(1 Pt 2): 233-239.
Ko FW, Tam W, Wong TW, Chan DP, Tung AH, Lai CK, et al. 2007b. Temporal relationship between air pollutants and hospital admissions for chronic obstructive pulmonary disease in Hong Kong. Thorax 62(9): 780-785.
Mayer AS, Newman LS. 2001. Genetic and environmental modulation of chronic obstructive pulmonary disease. Respir Physiol 128(1): 3-11.
Lin M, Stieb DM, Chen Y. 2005. Coarse particulate matter and hospitalization for respiratory infections in children younger than 15 years in Toronto: a case-crossover analysis. Pediatrics 116(2): e235-240.
Medina-Ramon M, Zanobetti A, Schwartz J. 2006. The effect of ozone and PM10 on hospital admissions for pneumonia and chronic obstructive pulmonary disease: a national multicity study. Am J Epidemiol 163(6): 579-588.
Laden F, Hart JE, Smith TJ, Davis ME, Garshick E. 2007. Cause-specific mortality in the unionized U.S. trucking industry. Environ Health Perspect 115(8): 1192-1196.
Pope CA, 3rd, Burnett RT, Thun MJ, Calle EE, Krewski D, Ito K, et al. 2002. Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. JAMA 287(9): 1132-1141.
Laden F, Neas LM, Dockery DW, Schwartz J. 2000. Association of fine particulate matter from different sources with daily mortality in six U.S. cities. Environ Health Perspect 108(10): 941-947.
Pope CA, 3rd, Thun MJ, Namboodiri MM, Dockery DW, Evans JS, Speizer FE, et al. 1995. Particulate air pollution as a predictor of mortality in a prospective study of U.S. adults. Am J Respir Crit Care Med 151(3 Pt 1): 669-674.
Donaldson K, Stone V, Clouter A, Renwick L, MacNee W. 2001. Ultrafine particles. Occup Environ Med 58(3): 211-216, 199.
Kaiser J. 2005. Epidemiology. Mounting evidence indicts fine-particle pollution. Science 307(5717): 1858-1861.
Tao F, Gonzalez-Flecha B, Kobzik L. 2003. Reactive oxygen species in pulmonary inflammation by ambient particulates. Free Radic Biol Med 35(4): 327-340.
Duffin R, Tran L, Brown D, Stone V, Donaldson K. 2007a. Proinflammogenic effects of low-toxicity and metal nanoparticles in vivo and in vitro: highlighting the role of particle surface area and surface reactivity. Inhal Toxicol 19(10): 849-856.
Kittelson D.B. WWF, Johnson J.P. 2004. Nanoparticle emissions on Minnesota highways. Atmospheric Environment 38: 9-19.
Donaldson K, Stone V. 2003. Current hypotheses on the mechanisms of toxicity of ultrafine particles. Ann Ist Super Sanita 39(3): 405-410.
Donaldson K, Tran L, Jimenez LA, Duffin R, Newby DE, Mills N, et al. 2005. Combustion-derived nanoparticles: a review of their toxicology following inhalation exposure. Part Fibre Toxicol 2: 10.
Duffin R, Mills NL, Donaldson K. 2007b. Nanoparticles-a thoracic toxicology perspective. Yonsei Med J 48(4): 561-572.
Holgate S. 1995. The nature of airborne particles. Non biological particles and health.Department of Health. The Committee on the Medical Effects of Air Pollutants (COMEAP).
Palmgren F. WP, Loft S. 2003. The Pollution of Air with Particles in Copenhagen. Ministry of the Environment, Copenhagen.
Chen KS, Lin CF, Chou YM. 2001. Determination of source contributions to ambient PM2.5 in Kaohsiung, Taiwan, using a receptor model. J Air Waste Manag Assoc 51(4): 489-498.
Cackovic M, Sega K, Vadic V, Beslic I, Soljic Z. 2001. Seasonal distributions of acid components in PM2.5 fraction of airborne particles in Zagreb air. Bull Environ Contam Toxicol 67(5): 704-711.
USEPA. 1995. Compilation of Air Pollutant Emission Factors. USEPA report AP-42, US Environmental Protection Agency, Washington, DC.
TNO. 1997. Particulate Mater Emissions (PM10, PM2.5 PM<0.1) in
Europe in 1990 and 1993. TNO report TNO-MEP-R96-472, TNO, Zeist, the Netherlands.
Birmili W, Allen AG, Bary F, Harrison RM. 2006. Trace metal concentrations and water solubility in size-fractionated atmospheric particles and influence of road traffic. Environ Sci Technol 40(4): 1144-1153.
Salma I, Maenhaut W. 2006. Changes in elemental composition and mass of atmospheric aerosol pollution between 1996 and 2002 in a Central European city. Environ Pollut 143(3): 479-488.
Oberdorster G, Oberdorster E, Oberdorster J. 2005. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113(7): 823-839.
Stone V, Shaw J, Brown DM, Macnee W, Faux SP, Donaldson K. 1998. The role of oxidative stress in the prolonged inhibitory effect of ultrafine carbon black on epithelial cell function. Toxicol In Vitro 12(6): 649-659.
Risom L, Moller P, Loft S. 2005. Oxidative stress-induced DNA damage by particulate air pollution. Mutat Res 592(1-2): 119-137.
Han JY, Takeshita K, Utsumi H. 2001. Noninvasive detection of hydroxyl radical generation in lung by diesel exhaust particles. Free Radic Biol Med 30(5): 516-525.
Ghio AJ, Richards JH, Carter JD, Madden MC. 2000. Accumulation of iron in the rat lung after tracheal instillation of diesel particles. Toxicol Pathol 28(4): 619-627.
Donaldson K, Beswick PH, Gilmour PS. 1996. Free radical activity associated with the surface of particles: a unifying factor in determining biological activity? Toxicol Lett 88(1-3): 293-298.
Zhang Q, Kusaka Y, Sato K, Nakakuki K, Kohyama N, Donaldson K. 1998. Differences in the extent of inflammation caused by intratracheal exposure to three ultrafine metals: role of free radicals. J Toxicol Environ Health A 53(6): 423-438.
Committee E. 1999. Getting Started: Emissions Inventory Methods For PM2.5.
Dominici F, Peng RD, Bell ML, Pham L, McDermott A, Zeger SL, et al. 2006. Fine particulate air pollution and hospital admission for cardiovascular and respiratory diseases. JAMA 295(10): 1127-1134.
von Klot S, Peters A, Aalto P, Bellander T, Berglind N, D'Ippoliti D, et al. 2005. Ambient air pollution is associated with increased risk of hospital cardiac readmissions of myocardial infarction survivors in five European cities. Circulation 112(20): 3073-3079.
Wellenius GA, Schwartz J, Mittleman MA. 2006. Particulate air pollution and hospital admissions for congestive heart failure in seven United States cities. Am J Cardiol 97(3): 404-408.
Pope CA, 3rd, Muhlestein JB, May HT, Renlund DG, Anderson JL, Horne BD. 2006. Ischemic heart disease events triggered by short-term exposure to fine particulate air pollution. Circulation 114(23): 2443-2448.
Devlin RB, Ghio AJ, Kehrl H, Sanders G, Cascio W. 2003. Elderly humans exposed to concentrated air pollution particles have decreased heart rate variability. Eur Respir J Suppl 40: 76s-80s.
Zanobetti A, Schwartz J. 2002. Cardiovascular damage by airborne particles: are diabetics more susceptible? Epidemiology 13(5): 588-592.
O'Neill MS, Veves A, Zanobetti A, Sarnat JA, Gold DR, Economides PA, et al. 2005. Diabetes enhances vulnerability to particulate air pollution-associated impairment in vascular reactivity and endothelial function. Circulation 111(22): 2913-2920.
Mills NL, Tornqvist H, Gonzalez MC, Vink E, Robinson SD, Soderberg S, et al. 2007. Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in men with coronary heart disease. N Engl J Med 357(11): 1075-1082.
Kodavanti UP, Moyer CF, Ledbetter AD, Schladweiler MC, Costa DL, Hauser R, et al. 2003. Inhaled environmental combustion particles cause myocardial injury in the Wistar Kyoto rat. Toxicol Sci 71(2): 237-245.
Cozzi E, Hazarika S, Stallings HW, 3rd, Cascio WE, Devlin RB, Lust RM, et al. 2006. Ultrafine particulate matter exposure augments ischemia-reperfusion injury in mice. Am J Physiol Heart Circ Physiol 291(2): H894-903.
Schirle M, Heurtier MA, Kuster B. 2003. Profiling core proteomes of human cell lines by one-dimensional PAGE and liquid chromatography-tandem mass spectrometry. Mol Cell Proteomics 2(12): 1297-1305.
Hirsch J, Hansen KC, Burlingame AL, Matthay MA. 2004. Proteomics: current techniques and potential applications to lung disease. Am J Physiol Lung Cell Mol Physiol 287(1): L1-23.
Ostrowski LE, Blackburn K, Radde KM, Moyer MB, Schlatzer DM, Moseley A, et al. 2002. A proteomic analysis of human cilia: identification of novel components. Mol Cell Proteomics 1(6): 451-465.
Hamilton RF, Jr., Holian A, Morandi MT. 2004. A comparison of asbestos and urban particulate matter in the in vitro modification of human alveolar macrophage antigen-presenting cell function. Exp Lung Res 30(2): 147-162.
van Eeden SF, Tan WC, Suwa T, Mukae H, Terashima T, Fujii T, et al. 2001. Cytokines involved in the systemic inflammatory response induced by exposure to particulate matter air pollutants (PM(10)). Am J Respir Crit Care Med 164(5): 826-830.
Rossi AG, Haslett C, Hirani N, Greening AP, Rahman I, Metz CN, et al. 1998. Human circulating eosinophils secrete macrophage migration inhibitory factor (MIF). Potential role in asthma. J Clin Invest 101(12): 2869-2874.
Kobayashi M, Nasuhara Y, Kamachi A, Tanino Y, Betsuyaku T, Yamaguchi E, et al. 2006. Role of macrophage migration inhibitory factor in ovalbumin-induced airway inflammation in rats. Eur Respir J 27(4): 726-734.
Cha MH, Rhim T, Kim KH, Jang AS, Paik YK, Park CS. 2007. Proteomic identification of macrophage migration-inhibitory factor upon exposure to TiO2 particles. Mol Cell Proteomics 6(1): 56-63.
Zhang S, Xu N, Nie J, Dong L, Li J, Tong J. 2008. Proteomic alteration in lung tissue of rats exposed to cigarette smoke. Toxicol Lett 178(3): 191-196.
Signor L, Tigani B, Beckmann N, Falchetto R, Stoeckli M. 2004. Two-dimensional electrophoresis protein profiling and identification in rat bronchoalveolar lavage fluid following allergen and endotoxin challenge. Proteomics 4(7): 2101-2110.
Tzivion G, Gupta VS, Kaplun L, Balan V. 2006. 14-3-3 proteins as potential oncogenes. Semin Cancer Biol 16(3): 203-213.
Porter GW, Khuri FR, Fu H. 2006. Dynamic 14-3-3/client protein interactions integrate survival and apoptotic pathways. Semin Cancer Biol 16(3): 193-202.
Hermeking H, Lengauer C, Polyak K, He TC, Zhang L, Thiagalingam S, et al. 1997. 14-3-3 sigma is a p53-regulated inhibitor of G2/M progression. Mol Cell 1(1): 3-11.
Aprelikova O, Pace AJ, Fang B, Koller BH, Liu ET. 2001. BRCA1 is a selective co-activator of 14-3-3 sigma gene transcription in mouse embryonic stem cells. J Biol Chem 276(28): 25647-25650.
Chan TA, Hermeking H, Lengauer C, Kinzler KW, Vogelstein B. 1999. 14-3-3Sigma is required to prevent mitotic catastrophe after DNA damage. Nature 401(6753): 616-620.
Laronga C, Yang HY, Neal C, Lee MH. 2000. Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression. J Biol Chem 275(30): 23106-23112.
Lodygin D, Hermeking H. 2006. Epigenetic silencing of 14-3-3sigma in cancer. Semin Cancer Biol 16(3): 214-224.
van Hemert MJ, Steensma HY, van Heusden GP. 2001. 14-3-3 proteins: key regulators of cell division, signalling and apoptosis. Bioessays 23(10): 936-946.
Niemantsverdriet M, Wagner K, Visser M, Backendorf C. 2008. Cellular functions of 14-3-3 zeta in apoptosis and cell adhesion emphasize its oncogenic character. Oncogene 27(9): 1315-1319.
Shoji M, Kawamoto S, Setoguchi Y, Mochizuki K, Honjoh T, Kato M, et al. 1994. The 14-3-3 protein as the antigen for lung cancer-associated human monoclonal antibody AE6F4. Hum Antibodies Hybridomas 5(3-4): 123-130.
Qi W, Liu X, Qiao D, Martinez JD. 2005. Isoform-specific expression of 14-3-3 proteins in human lung cancer tissues. Int J Cancer 113(3): 359-363.
Arora S, Matta A, Shukla NK, Deo SV, Ralhan R. 2005. Identification of differentially expressed genes in oral squamous cell carcinoma. Mol Carcinog 42(2): 97-108.
Jang JS, Cho HY, Lee YJ, Ha WS, Kim HW. 2004. The differential proteome profile of stomach cancer: identification of the biomarker candidates. Oncol Res 14(10): 491-499.
Zang L, Palmer Toy D, Hancock WS, Sgroi DC, Karger BL. 2004. Proteomic analysis of ductal carcinoma of the breast using laser capture microdissection, LC-MS, and 16O/18O isotopic labeling. J Proteome Res 3(3): 604-612.
Somiari RI, Somiari S, Russell S, Shriver CD. 2005. Proteomics of breast carcinoma. J Chromatogr B Analyt Technol Biomed Life Sci 815(1-2): 215-225.
Li Z, Zhao J, Du Y, Park HR, Sun SY, Bernal-Mizrachi L, et al. 2008. Down-regulation of 14-3-3zeta suppresses anchorage-independent growth of lung cancer cells through anoikis activation. Proc Natl Acad Sci U S A 105(1): 162-167.
Peters A, Dockery DW, Muller JE, Mittleman MA. 2001. Increased particulate air pollution and the triggering of myocardial infarction. Circulation 103(23): 2810-2815.
Peters A, von Klot S, Heier M, Trentinaglia I, Hormann A, Wichmann HE, et al. 2004. Exposure to traffic and the onset of myocardial infarction. N Engl J Med 351(17): 1721-1730.
Gong H, Jr., Linn WS, Sioutas C, Terrell SL, Clark KW, Anderson KR, et al. 2003. Controlled exposures of healthy and asthmatic volunteers to concentrated ambient fine particles in Los Angeles. Inhal Toxicol 15(4): 305-325.
Urch B, Silverman F, Corey P, Brook JR, Lukic KZ, Rajagopalan S, et al. 2005. Acute blood pressure responses in healthy adults during controlled air pollution exposures. Environ Health Perspect 113(8): 1052-1055.
Touyz RM, Schiffrin EL. 2000. Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells. Pharmacol Rev 52(4): 639-672.
Kimura K, Eguchi S. 2009. Angiotensin II type-1 receptor regulates RhoA and Rho-kinase/ROCK activation via multiple mechanisms. Focus on "Angiotensin II induces RhoA activation through SHP2-dependent dephosphorylation of the RhoGAP p190A in vascular smooth muscle cells". Am J Physiol Cell Physiol 297(5): C1059-1061.
Sun Q, Yue P, Ying Z, Cardounel AJ, Brook RD, Devlin R, et al. 2008. Air pollution exposure potentiates hypertension through reactive oxygen species-mediated activation of Rho/ROCK. Arterioscler Thromb Vasc Biol 28(10): 1760-1766.
Bian YL, Qi YX, Yan ZQ, Long DK, Shen BR, Jiang ZL. 2008. A proteomic analysis of aorta from spontaneously hypertensive rat: RhoGDI alpha upregulation by angiotensin II via AT(1) receptor. Eur J Cell Biol 87(2): 101-110.
Lee DL, Webb RC, Jin L. 2004. Hypertension and RhoA/Rho-kinase signaling in the vasculature: highlights from the recent literature. Hypertension 44(6): 796-799.
Hassanain HH, Gregg D, Marcelo ML, Zweier JL, Souza HP, Selvakumar B, et al. 2007. Hypertension caused by transgenic overexpression of Rac1. Antioxid Redox Signal 9(1): 91-100.
van Nieuw Amerongen GP, van Hinsbergh VW. 2001. Cytoskeletal effects of rho-like small guanine nucleotide-binding proteins in the vascular system. Arterioscler Thromb Vasc Biol 21(3): 300-311.
Dustin ML, Rothlein R, Bhan AK, Dinarello CA, Springer TA. 1986. Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol 137(1): 245-254.
Leeuwenberg JF, Smeets EF, Neefjes JJ, Shaffer MA, Cinek T, Jeunhomme TM, et al. 1992. E-selectin and intercellular adhesion molecule-1 are released by activated human endothelial cells in vitro. Immunology 77(4): 543-549.
Strieter RM, Kunkel SL. 1994. Acute lung injury: the role of cytokines in the elicitation of neutrophils. J Investig Med 42(4): 640-651.
Koslowski R, Dobbs LG, Wenzel KW, Schuh D, Muller M, Kasper M. 1998. Loss of immunoreactivity for RTI40, a type I cell-specific protein in the alveolar epithelium of rat lungs with bleomycin-induced fibrosis. Eur Respir J 12(6): 1397-1403.
Barton WW, Wilcoxen SE, Christensen PJ, Paine R, 3rd. 1996. Association of ICAM-1 with the cytoskeleton in rat alveolar epithelial cells in primary culture. Am J Physiol 271(5 Pt 1): L707-718.
Paine R, 3rd, Morris SB, Jin H, Baleeiro CE, Wilcoxen SE. 2002. ICAM-1 facilitates alveolar macrophage phagocytic activity through effects on migration over the AEC surface. Am J Physiol Lung Cell Mol Physiol 283(1): L180-187.
Kang BH, Crapo JD, Wegner CD, Letts LG, Chang LY. 1993. Intercellular adhesion molecule-1 expression on the alveolar epithelium and its modification by hyperoxia. Am J Respir Cell Mol Biol 9(4): 350-355.
Burns AR, Takei F, Doerschuk CM. 1994. Quantitation of ICAM-1 expression in mouse lung during pneumonia. J Immunol 153(7): 3189-3198.
Barton WW, Wilcoxen S, Christensen PJ, Paine R. 1995. Disparate cytokine regulation of ICAM-1 in rat alveolar epithelial cells and pulmonary endothelial cells in vitro. Am J Physiol 269(1 Pt 1): L127-135.
Bevilacqua MP. 1993. Endothelial-leukocyte adhesion molecules. Annu Rev Immunol 11: 767-804.
Panes J, Perry MA, Anderson DC, Manning A, Leone B, Cepinskas G, et al. 1995. Regional differences in constitutive and induced ICAM-1 expression in vivo. Am J Physiol 269(6 Pt 2): H1955-1964.
Lyons PD, Benveniste EN. 1998. Cleavage of membrane-associated ICAM-1 from astrocytes: involvement of a metalloprotease. Glia 22(2): 103-112.
van de Stolpe A, van der Saag PT. 1996. Intercellular adhesion molecule-1. J Mol Med (Berl) 74(1): 13-33.
Conner ER, Ware LB, Modin G, Matthay MA. 1999. Elevated pulmonary edema fluid concentrations of soluble intercellular adhesion molecule-1 in patients with acute lung injury: biological and clinical significance. Chest 116(1 Suppl): 83S-84S.
Kasper M, Koslowski R, Luther T, Schuh D, Muller M, Wenzel KW. 1995. Immunohistochemical evidence for loss of ICAM-1 by alveolar epithelial cells in pulmonary fibrosis. Histochem Cell Biol 104(5): 397-405.
Mendez MP, Morris SB, Wilcoxen S, Greeson E, Moore B, Paine R, 3rd. 2006. Shedding of soluble ICAM-1 into the alveolar space in murine models of acute lung injury. Am J Physiol Lung Cell Mol Physiol 290(5): L962-970.
Budnik A, Grewe M, Gyufko K, Krutmann J. 1996. Analysis of the production of soluble ICAM-1 molecules by human cells. Exp Hematol 24(2): 352-359.
Endo S, Inada K, Kasai T, Takakuwa T, Yamada Y, Koike S, et al. 1995. Levels of soluble adhesion molecules and cytokines in patients with septic multiple organ failure. J Inflamm 46(4): 212-219.
Schmal H, Czermak BJ, Lentsch AB, Bless NM, Beck-Schimmer B, Friedl HP, et al. 1998. Soluble ICAM-1 activates lung macrophages and enhances lung injury. J Immunol 161(7): 3685-3693.
論文全文使用權限
  • 同意授權校內瀏覽/列印電子全文服務,於2022-12-31起公開。


  • 如您有疑問,請聯絡圖書館
    聯絡電話:(06)2757575#65773
    聯絡E-mail:etds@email.ncku.edu.tw