(3.239.33.139) 您好!臺灣時間:2021/03/08 18:15
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:謝宛伶
研究生(外文):Hsieh, Wan-Ling
論文名稱:探討血液急性蛋白Haptoglobin在運動後增加之生理角色與其機制
論文名稱(外文):Plasma haptoglobin is an acute-phase protein responsive to exercise: A physiologic role and its mechanism involved
指導教授:毛仁淡
指導教授(外文):Mao, Simon J.T.
學位類別:碩士
校院名稱:國立交通大學
系所名稱:分子醫學與生物工程研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2010
畢業學年度:98
語文別:中文
論文頁數:45
中文關鍵詞:急性蛋白
外文關鍵詞:acute phase protein
相關次數:
  • 被引用被引用:0
  • 點閱點閱:171
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
Haptoglobin簡稱為Hp,是一個抗發炎以及抗氧化的分子,主要由肝臟以及肺臟合成,當身體發炎以及遭受感染時血液中Hp會大量上升。Hp在體內最主要的功能為,當在紅血球發生溶血時Hp能和清除多餘的含鐵離子之血色素,避免產生過多的自由基。
在短暫且激烈的運動過後,體內氧化壓力會大量上升,所以我們提出了一個假說: 為了要減少體內氧化壓力的產生,運動後血液中Hp的濃度會提高。二十四隻實驗小鼠分為四個組別,連續被動運動零週、一週、二週和三週。首先我們發現運動後Hp在血液中濃度會上升,並且在運動三週之嗜中性球數目顯著增加(P&;lt;0.05)。有趣的是,被認為是Hp主要來源的肝臟,Hp基因表現量無差異,因此推測嗜中性球是運動後血液Hp升高的來源。由於Hp是一個強力的抗氧化物,推測在運動過程中Hp可以減少氧化壓力的產生,扮演著保護身體的角色。

Haptoglobin (Hp), an anti-inflammatory and antioxidant molecule, is primarily synthesized in lung and liver and sharply increases during inflammation or infection. One of the major functions of Hp is to scavenge the free radicals produced from Fe3+-hemoglobin following the hemolysis of red blood cells.
Because after a short-term bout of exhaustive exercise is usually associated oxidative stress, we tested a hypothesis that exercise may elevate plasma Hp in order to reduce the resulting oxidative stress. Mice (n=24) were divided into four groups with 0, 1-, 2 and 3- week passive exercise. First, we demonstrated for the first time that plasma Hp increased substantially overtime following the exercise. Next, we showed neutrophil being significantly increased after three-week exercise (p<0.05). Interestingly, the Hp mRNA of liver, a major organ for Hp synthesis, remained unchanged. Thus, the data indicate that exercise may induce the plasma Hp levels by primarily using neutrophils as a source. Because Hp is an extremely potent antioxidant, the present study suggests that elevated Hp may play a potentially protective role to reduce the oxidative stress during the exercise.

中文摘要 i
Abstract ii
誌謝 iii
表目錄 vi
圖目錄 vii
第一章 緒論 1
1-1、 Hp在染色體上的分布 1
1-2、 Hp之表現型及人口分佈 1
1-3、 Hp生理功能之探討 2
1-3.1. Hp抗氧化能力 2
1-3.2. Hp調節免疫反應及發炎 3
1-4、 Hp與臨床疾病之相關性 4
1-5、 運動與細胞免疫系統 5
1-5.1. 白血球的增生和運輸 5
1-5.2. 嗜中性球之功能 6
1-5.3. 運動與細胞激素 6
1-6、 運動與氧化壓力 7
1-7、 運動與臨床疾病相關性 8
1-8、 研究目的 8
第二章 材料 9
2-1、 實驗材料 9
2-2、 實驗儀器 10
第三章 方法 11
3-1、 被動式運動策略 11
3-2、 實驗方法 11
3-2.1. 核醣核酸萃取 11
3-2.2. 反轉錄PCR 11
3-2.3. 聚合酶連鎖反應 12
3-2.4. Hp類型鑑定膠 13
3-2.5. 西方墨點法 13
3-2.6. 細胞免疫染色 14
3-2.7. 純化血紅素 15
3-2.8. 統計方法 15
第四章 結果與討論 16
4-1、 探討運動後Hp在血漿中的表現量 16
4-2、 探討白血球Hp基因以及細胞激素基因的表現量 16
4-3、 臟器中Hp 基因表現量 17
4-4、 白血球全血分析 17
4-5、 利用免疫染色探討Hp在白血球族群的分布 18
第五章 結論 19
參考文獻 20

Abdullah M., Schultz H., Kähler D., Branscheid D., Dalhoff K., Zabel P., Vollmer E. and Goldmann T. Expression of the acute phase protein haptoglobin in human lung cancer and tumor-free lung tissues. Pathol Res Pract 2009; 205:6396-47.

Arredouani MS., Kasran A., Vanoirbeek JA., Berger FG., Baumann H and Ceuppens JL. Haptoglobin dampens endotoxin-induced inflammatroy effects both in vitro and in vivo. Immunology 2005; 112:263-271

Atkinson SH., Mwangi TW., Uyoga SM., Ogada E., Macharia, AW., Marsh K., Prentice AM and Williams TN. The haptoglobin 2-2 genotype is associated with a reduced incidence of Plasmodium falciparum malaria in children on the coast of Kenya. Clin Infect Dis 2007; 44:802—809.

Avloniti AA., Douda HT., Tokmakidis SP., Kortsaris AH., Papadopoulou EG.,
Spanoudakis EG. Acute effects of soccer training on white blood cell count in elite female players. Int J Sports Physiol Perform 2007; 3:239-249.

Balla J., Jacob HS., Balla G., Nath K., Eaton JW. and Vercelotti GM. Endothelial-cell heme uptake from heme proteins: induction of sensitization and desensitization to oxidant damage. Proc Natl Acad Sci USA 1993; 90:9285-9289.

Beisembaeva RU., Dzhumalieva LM., Shaikenov TE. and Mevkh AT.Identification of haptoglobin as an endogenous inhibitor of prostaglandin H synthase in the cytosol fraction of primary cells from sheep vesicular glands. FEBS Lett 1990; 269: 125-127.

Pedersen BK. and Hoffman-Goetz L. Exercise and the Immune System: Regulation, Integration, and Adaptation. Physiol Rev 2000; 80:1055-1081.

Berk LS.,Tan SA.,Nieman DC. and Edy WC. The suppressive effect of stress from acute exhaustive exercise on T-lymphocyte helper/suppressor ratio in athletes and non-athletes. Med & Sci Sport & Exer 1986; 17:492.

Blair SN., Cheng Y. and Holder JS. Is physical activity or physical fitness more important in defining health benefits? Med Sci Sports Exerc 2001; 33:379–399.

Bowman BH. and Kurosky A. Haptoglobin: the evolutionary product of duplication, unequal crossing over, and point mutation. Adv Human Genet 1982; 12: 189-261.

Bowman BH. Haptoglobin. In: Bowman BH, ed. Hepatic plasma proteins. San Diego: Academic Press 1993: 159-167.

Costacou T., Ferrell RE and Orchard TJ. Haptoglobin genotype: a determinant of cardiovascular complication risk in type 1 diabetes. Diabetes 2008; 57:1702-1706.

Cheng TM., Larsson M., Chou FH., SJT Mao and Chang CC. Unique assembly structure of human haptoglobin phenotypes 1-1, 2-1and 2-2 and a predominant Hp1 allele Hypothesis. Biophysical J 2009; 96:586.


Delanghe J., Cambier B., Langlois M., De Buyzere M., Neels H., De Bacquer D. and Van Cauwelaert P. Haptoglobin polymorphism, a genetic risk factor in coronary bypass surgery. Atherosclerosis 1997; 132:215-219.

Delanghe J., Duprez D., De Buyzere., Bergez B., Callens B., Leroux-Roels G. and Clement D. Haptoglobin phenotypes and complications in established essential arterial hypertension. J Hypertens 1993; 11:861-867.

Desilets A., Gheorghiu I., Yu SJ., Seidman EG. and Asselin, C. Inhibition by deacetylase inhibitors of IL-1-dependent induction of haptoglobin involves CCAAT/enhancerbinding protein isoforms in intestinal epithelial cells. Biochem Biophys Res Commun 2000; 276:673-679.

El Ghmati SM., Van Hoeyvald., Van Strijp JAG., Ceuppens JL. And Stevens EAM. Identification of haptoglobin as an alternative ligand for CD11b/CD18. J Immunol 1996; 156:2542-2552.

Erickson LM. and Maeda N. Junctions between genes in the haptoglobin gene cluster of primates. Genomics 1992; 14:948-958.

Febbraio MA and Pedersen BK. Muscle-derived interleukin-6: mechanisms for activation and possible biological roles. FASEB J Physiol 2003; 549:607-612.

Fedoseeva SV., Lusopova VP. and Pospelov LE. Course of infiltrating pulmonary tuberculosis depending on the patient’s genotype. Probl Tuberk 1993; 12:8-10.

Fernandez AZ., Lopez F., Tablante A., Romano E., Hurt-Camejo E.,Camejo G. and Apitz-Castro R. Intravascular hemolysis increases atherogenicity of diet-induced hypercholesterolemia in rabbits in spite of heme oxygenase-1 gene and protein induction. Atherosclerosis 2001; 158:103–111.

Gabriel H. and Kindermann W. The acute immune response to exercise: what does it mean? Int J Sports Med 1997; 18: 28-45.

Gleeson M. Interleukins and exercise. J. Physiol. 2000; 15:529.

Gleeson M., McFarlin BK and Flynn MG. Exercise and Toll-like receptors. Exerc Immunol Rev 2006; 12:34-53.

Goldhammer E., Tanchilevitch A., Maor I., Beniamini Y., Rosenschein U., Sagiv M. Exercise training modulates cytokine activity in coronary heart disease patients. Int J Cardiol 2005; 100:93-99.

Guetta J., Strauss M., Levy NS., Fahoum L and Levy AP.Haptoglobin genotype modulates the balance of Th1/Th2 cytyokines produced by macrophages exposed to free hemoglobin. Atherosclerosis 2007; 191:48-53.

Gulmez O., Ertan C., Yildirir A., Konas D., Bal U., Aydinalp A., Demir O., Ozin B and Muderrisoglu H. C-reactive protein levels increase after exercise testing in patients with increased platelet reactivity. Coron Artery Dis 2007; 18:437-42.

Quaye IK. Haptoglobin, inflammation and disease. Trans R Soc Trop Med Hyg 2008; 102:735-742.

Jolliffe JA., Rees K.,Taylor RS., Thompson D., Oldridge N., and Ebrahim S. Exercise-based rehabilitation for coronary heart disease. Cochrane Database Syst Rev 2000; 4: CD001800.

Jonsdottir I., Schjerling P., Ostrowski K., Asp S., Richter EA. and Pedersen BK .Muscle contractions induces interleukin-6 mRNA production in rat skeletal muscles J Physiol 2000; 528: 157–163.

Keller C., Steensberg A., Pilegaard H., Osada T., Saltin B., Pedersen BK. and Neufer PD. Transcriptional activation of the IL-6 gene in human contracting skeletal muscle: influence of muscle glycogen content. FASEB J 2001; 15:2748–2750.

Lockhart NC. and Brooks SV. Neutrophil accumulation following passive stretches contributes to adaptations that reduce contraction-induced skeletal muscle injury in mice. J Appl Physicol 2008;104:1109-1115.

Miyoshi E. and Nakano M. Fucosylated haptoglobin is a novel marker for pancreatic cancer: detailed analyses of oligosaccharide structures. Proteomics 2008; 8:3257-62.

Okuyama N., Ide Y., Nakano M., Nakagawa T., Yamanaka K., Moriwaki K., Murata K., Ohigashi H., Yokoyama S., Eguchi H., Ishikawa O., Ito T., Kato M., Kasahara A., Kawano S., Gu J., Taniguchi N. and Miyoshi E. Fucosylated haptoglobin is a novel marker for pancreatic cancer: a detailed analysis of the oligosaccharide structure and a possible mechanism for fucosylation. Int J Cancer 2006; 118:2803-8.

Pabst R. The spleen in lymphocyte migration. Immunol Today 1988; 9:43-45.

Peake J., Wilson G., Hordern M., Suzuki K., Yamaya K., Nosaka K., Mackinnon L and Coombes JS. Changes in neutrophil surface receptor expression, degranulation, andrespiratory burst activity after moderate- and high-intensity exercise. J Appl Physiol 2004;97:612-618.

Pedersen BK., Akerström TC., Nielsen AR. and Fischer CP. Role of myokines in exercise and metabolism. J Appl Physol 2007;103:1093-1098.

Pedersen BK., Steensberg A. and Schjerling P. Muscle derived interleukin-6: possible biological effects. J Physiol 2001; 536:329-337.

Penkowa M., Keller C., Keller P., Jauffred S. and Pedersen BK. Immunohistochemical detection of interleukin-6 in human skeletal muscle fibers following exercise. FASEB J 2003; 17:2166–2168.

Petersen AMW. , Pedersen BK. The anti-inflammatroy effect of exercise. J Appl Physiol 2005; 98:1154-1162.

Pizza FX., Koh TJ., McGregor SJ. and Brooks SV. Muscle inflammatory cells after passive stretches, isometric contractions, and lengthening contractions. J Appl Physiol 2002; 92:1873-1878.

Pue CA., Mortensen RF., Marsh CB., Pope HA., and Wewers MD. Acute phase levels of C-reactive protein enhance IL-1 beta and IL-1ra production by human blood monocytes but inhibit IL-1 beta and IL-1ra production by alveolar macrophages. J Immunol 1996; 156:1594–1600.

Radom-Aizik S., Zaldivar F Jr., Leu SY.,Galassetti P and Cooper DM. Effects of 30 min of aerobic exercise on gene expression in human neutrophils. J Appl Physicol 2008; 104:236-243.

Saeed S A., Ahmad N., Ahmed S. Dual inhibition of cyclooxygenase and lipoxygenase by human haptoglobin: Its polymorphism and relation to hemoglobin binding. Biochem Biophys Res Commun 2007; 353:915—920.

Salvatore A., Cigliano L., Bucci EM., Corpillo D., Velasco S., Carlucci A., Pedone C and Abrescia,P . Haptoglobin binding to apolipoprotein A-I prevents damage from hydroxyl radicals on its stimulatory activity of the enzyme lecithin-cholesterol acyltransferase. Biochemistry 2007; 46: 11158—11168.

Shah A., Singh H., Sachdev V., Lee J., Yotsukura S., Salgia R., Bharti A. Differential serum level of specific haptoglobin isoforms in small cell lung cancer. Curr Proteomics 2010; 7:49-65.

Shephard R. Sepsis and mechanisms of inflammatory response: is exercise a good model? Br J Sports Med 2001; 35:223–230.

Smeets MB., Sluijter JP., Donners MM., Velema E., Heeneman S., Pasterkamp G. and de Kleijn DP. Increased arterial expression of a glycosylated haptoglobin isoform after balloon dilation. Cardiovasc Res 2003; 58:689-695.

Steensberg A., Febbraio MA., Osada T., Schjerling P., van Hall G., Saltin B. and Pedersen BK. Interleukin-6 production in contracting human skeletal muscle is influenced by pre-exercise muscle glycogen content. J Physiol 2001; 537:633–639.

Steensberg A., Hall GV., Osada T., Sacchetti M., Saltin B and Pedersen BK. Production of interleukin-6 in contracting human skeletal muscles can account for the exercise induce increase in plasma interleukin-6. J Physiol 2000; 529:237–242.

Theilgaard-Monch K., Jacobsen LC., Nielsen MJ., Rasmussen T.,Udby L., Gharib M., Arkwright PD., Gombart AF., Calafat J., Moestrup SK., Porse BT and Borregaard N. Haptoglobin is synthesized during granulocyte differentiation, stored in specific granules, and released by neutrophils in response to activation. Blood 2006; 108:353-361.

Thompson PD. Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease. Arterioscler Thromb Vasc Biol. 2003; 8:1319-1321.

Gutteridge JMC. The antioxidant activity of Haptoglobin towards haemoglobin-stimulated lipid peroxidation. Biochim Biophys Acta 1987; 917:219-223.

Haber F. and Weiss J. The catalytic decomposition of hydrogen peroxide by iron salts. Proc R Soc A 1934; 147:332-351.

Hanasaki K., Powell LD. and Varki A. Binding of human sialoglycoproteins by the B-cell specfic lectin CD22. selective recognition of immunoglobulin M and haptoglobin. J Biol Chem 1995; 270:7543-7550.

Javid J. The effect of haptoglobin-polymer size on hemoglobin binding capacity. Vox Sang 1965; 10:320-325.

Kasvosve I., Gomo ZA., Mvundura E., Moyo VM., Saungweme T., Khumalo H., Gordeuk VR., Boelaert JR., Delanghe JR., De Bacquer D. and Gangaidzo IT. Haptoglobin polymorphism and mortality in patients with tuberculosis. Int J Tuberc Lung Dis 2000; 4:771-775.

Kristlansen M., Graversen JH., Jacobsen C., Sonne O., Hoffman HJ., Law SKA. and Moestrup SK. Identification of the haemoglobin scavenger receptor. Nature 2001; 409:198-201.

Langlois MR. and Delanghe JR. Biological and clinical significance of haptoglobin polymorphism in humans. Clin Chem 1996; 42:1589-1600.

Leeuwenburgh C. and Heinecke J. Oxidative stress and antioxidants in exercise. Curr Med Chem 2001; 8: 829-838.

Levy AP., Roguin A., Hochberg I., Herer P., Marsh S., Nakhoul FM., and Skorecki K. Haptoglobin phenotype and vascular complications in patients with diabetes. N Engl J Med 2000; 343:969-970.

Loftus BJ., K. U-J., Senddon VP., Kalush F., Brandon R. and Fuhrmann J. Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q. Genomics 1999; 60:295-308.

Madsen MGJ. and Moestrup SK. Haptoglobin and CD163: captor and receptor gating hemoglobin to macrophage lysosomes. Redox Rep 2001; 6:386-388.
Maeda N., Barnett DR., Bowman BH. and Smithies O. Duplication within the haptoglobin Hp2 gene. Nature 1984; 309:131-135.

Melamed-Frank M., Lache O., Enav BI., Szafranek T., Levy NS., Ricklis RM. and Levy AP. Structure-function analysis of the antioxidant properties of haptoglobin. Blood 2001; 98:3693-3698.

Michel RL. and Joris RD. Biological and clinical significance of haptoglobin polymorphism in humans. Clin Chem 1996; 42:1589-1600.

Miller YI., Altamentova SM. and Shaklai N. Oxidation of low-density lipoprotein stem from a heme-initiated globin radical: antioxidant role of haptoglobin. Biochem 1997; 36:12189-12198.

Padma T. and Valli VV. ABO blood groups, intestinal alkaline phosphatase and haptoglobin types in patients with serum hepatitis. Hum Hered 1988; 38:367-371.

Philippidis P., Mason JC., Evansm BJ., Nadra I., Taylor KM., Haskard DO. and Landis RC. Hemoglobin scavenger receptor CD163 mediates Interleukin-10 release and heme oxygenase-1 synthesis: anti-inflammatory monocyte-macrophage responses in vitro, in resolving skin blisters in vivo, and after cardiopulmonary bypass surgery. Circ Res 2004; 94:119-126.

Quero C., Colome N., Prieto MR., Carrascal M., Posada M., Gelpi E. and Abian J. Determination of protein markers in human serum: Analysis of protein expression in toxic oil syndrome studies. Proteomics 2004; 4:303-315.

Rodriguez C., Quero C., Dominguez A., Trigo M., Posada de la Paz M., Glpi E. and Abian J. Proteomics 2006; 6:1-10.

Sadrzadeh SMH., Graf E., Panter SS., Hallaway PE. and Eaton JW. Hemoglobin – a biologic Fenton reagent. J Biol Chem 1984; 259:14354-14356.

Sinz A., Mikkat S., Ringel B., Dryynda S., Kekow J., Thiesen HJ. And Glocker MO. Mass spectrometric promteome analyses of synovial fluids and plasmas from patients suffering from rheumatoid arthritis and comparison to reactive arthritis or osteoarthritis. Electrophoresis 2002; 23:3445-3456.

Sjodin B., Hellsten WY. and Apple FS. Biochemical mechanisms for oxygen free radical formation during exercise. Sports Med 1990; 10:236-254.

Smithies O. Zone electrophoresis in starch gels: group variations in the serum proteins of normal human adults. Biochem J 1955; 61:629-641.

Stewart LK., Flynn MG., Campbell WW., Craig BA., Robinson JP., Mcfarlin BK., Timmerman KL., Coen PM., Felker J. and Talbert E. Influence of exercise training and age on CD14+ cell-surface expression of toll-like receptor 2 and 4. Brain Behav Immun 2005; 19:389-397.

Tolosano E., Fagoonee S., Hirsch E., Berger FG., Baumann H., Silengo L. and Altruda F. Enhanced splenomegaly and severe liver inflammation in aptoglobin/hemopexin double-null mice after acute hemolysis. Blood 2002; 100:4201-4208.

Tseng CF, Huang HY., Yang YT. and Mao SJT. Purification of human haptoglobin 1-1, 2-1, and 2-2 using monoclonal antibody affinity chromatography, Protein Expr Purif 2004; 33:265-273.

Tseng CF. and Mao SJT. Analysis of antioxidant as a therapeutic agent for atherosclerosis. Curr Pharm Analysis. 2006; 2:369-384

Tseng CF., Lin. CC., Huang. HY., Liu. HC. and Mao SJT. Antioxidant role of human haptoglobin. Proteomics 2004; 4:2221-2228.

Van Vlierberghe H., Langlois M. and Delanghe J. Haptoglobin polymorphisms and iron homeostasis in health and in disease. Clin Chim Acta 2004; 345:35-42.

Vider J., Lehtmaa J., Kullisaar T., Vihalemm T., Zilmer K., Kairane C., Landõr A., Karu T and Zilmer M. Acute immune response in respect to exercise induced oxidative stress. Pathophysiology 2001; 4:263-270.

Wallenius V., Wallenius K., Ahren B., Rudling M., Carlsten H., Dickson SL., Ohlsson C. and Jansson J. Interleukin-6- deficient mice develop mature-onset obesity. Nat Med 2002; 8:75-79.

Warner L., Gessl A., Baumgartner PS., Base W., Waldhausl W. and Pasternack MS. Haptoglobinphenotyping by newly developed monoclonal antibodies. Demmonstration of haptoglobin uptake into peripheral blood neutrophils and monocytes. J Immunol 1996; 156:1989-1996.

Wood JA., Lu Q and Lowder. Special feature for the Olympics: effects of exercise on the immune system: exercise induced modulationof macrophage function. Immunol cell 2000; 78:545-553.

Wu HJ., Chen KT., Shee BW., Chang HC., Huang YJ., Yang RS. Effects of 24 h ultra-marathon on biochemical and hematological parameters. World J Gastroenterol 2004; 10:2711-2714.

Yang F., Ghio AJ., Herbert DC., Weaker FJ., Water, CA. and Coalson JJ. Pulmonary expression of the human haptoglobin gene. Am J Respir Cell Mol Biol 2002; 23: 277-282.

連結至畢業學校之論文網頁點我開啟連結
註: 此連結為研究生畢業學校所提供,不一定有電子全文可供下載,若連結有誤,請點選上方之〝勘誤回報〞功能,我們會盡快修正,謝謝!
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔