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細胞外基質 ( Extracellular matrix, ECM ) & 細胞死亡

100BMC 短講 -. 細胞外基質 ( Extracellular matrix, ECM ) & 細胞死亡. Advisor: Hsien-Chang Chang Speaker: 連啟翔 (D2) date: 100.11.09. 細胞外基質 (Extracellular matrix, ECM). 膠原蛋白 Collagen. 玻尿酸 Hyaluronic acid. 彈力蛋白 Elastin. 纖維蛋白 Fibronectin. 附著複合物 (Focal adhesion complex). 蛋白醣大分子 (Proteoglycans).

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細胞外基質 ( Extracellular matrix, ECM ) & 細胞死亡

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  1. 100BMC短講- 細胞外基質( Extracellular matrix, ECM )&細胞死亡 Advisor: Hsien-Chang Chang Speaker: 連啟翔 (D2) date: 100.11.09

  2. 細胞外基質(Extracellular matrix, ECM) 膠原蛋白Collagen 玻尿酸Hyaluronic acid 彈力蛋白Elastin 纖維蛋白Fibronectin 附著複合物(Focal adhesion complex) 蛋白醣大分子(Proteoglycans) 結構性蛋白：膠原蛋白、彈力蛋白、纖維蛋白等 分泌 細胞 網狀結構 蛋白醣大分子

  3. Two main classes of ECM molecules • Fibrous proteins:- collagen, elastin, fibronectin, laminin. • Proteoglycans:- complex proteins and long chains of repeating disaccharide units called glycosaminoglycans (GAGs) GAGs, such as: ChondroitinSulfate Dermatan Sulfate Heparin Heparan Sulfate Hyaluronic Acid Keratan Sulfate). Fig. 2. - p.263

  4. 醣類 一 、成分： (1)醣類是由碳、氫、氧三種元素所組成。且多數的醣類， 其氫、氧之比例與水一樣，故又稱為碳水化合物。 (2)醣與糖的區別，在於「醣」即泛指所有的碳水化合物，如肝醣、纖維質、澱粉等；而「糖」是指具有甜味的醣類，如葡萄糖、麥芽糖等。 二、來源：醣類主要來自於植物經由「光合作用」，在葉綠體中合成。 三、分類：醣類根據其水解產物大致可分為四類： 單醣類、雙醣類、寡醣類、多醣類。

  5. 總整理 葡萄糖(Glucose) 蔗糖(Sucrose) 半乳糖 (Galactose) 乳糖 (Lactose) 果糖(Fructose) 麥芽糖(Maltose)

  6. Glycoproteinvs.Proteoglycan 定義 http://www.ilo.org/safework_bookshelf/english?image.gif&nd=857170059&src=857400144_files%2Fimage004.gif 特點 分布 http://www.funhousefilms.com/glycolip.jpg

  7. 蛋白聚醣 Proteoglycans 軟骨素 N-acetylglucosamine (乙醯葡萄糖胺) core protein Amino sugar 角質素 N-acetylgalactosamine (乙醯半乳糖胺) Glycosaminoglycans (GAGs) Glucuronic acid (葡萄糖醛酸) Uronic acid iduronic acid (艾杜醣醛酸) ☻composition - Unbranchespolysaccharides chains - Repeatingdisaccharideunits http://bjr.birjournals.org/cgi/content-nw/full/76/911/777/F1

  8. ☻Types- different Glycosaminoglycans (GAGs) ChondroitinSulfate Keratan Sulfate Dermatan Sulfate Hyaluronic Acid Heparin

  9. ☻Synthesis Heparan Sulfate with a neutral PH an acid environment 高基氏體 (木糖) (半乳糖) (葡萄糖醛酸) (絲胺酸) http://www.glycoforum.gr.jp/science/word/proteoglycan/PGA11E.html

  10. ☻Disease–Mucopolysaccharidoses (黏多醣症) • genetic disorders (autosomal recessive) • The inactivity of specific lysozomal enzymes that normally degrade glycosaminoglycans leads to the accumulation of proteoglycans within cells. 臨床特徵：此症患者出生時並無異樣，但隨著黏多醣日漸堆積，會逐漸出現各種症狀：身材矮小長不高、頭顱變大、濃眉、臉部身體多毛、鼻樑塌陷、嘴唇厚實。 關節變形僵硬、手臂粗短彎曲、爪狀手、短下肢、膝內翻、脊柱變粗。 肝脾腫大、腹部突出、肚臍疝氣、腹股溝疝氣、角膜混濁等。 http://www.netterimages.com/image/47151.htm

  11. Fibrous proteins - Collagen • - Major proteins of the ECM • Secreting by connective tissue cells（major fibroblast） • - Major component of skin and bone Glycine-X-Y X-Y: commonly proline or hydroproline

  12. The structure of collagen (膠原蛋白) • Collagen fibers as seen SEM. • A collagen fiber contains many fibrils, each of which is a kindle of collagen molecules, also called tropocollagen - Major proteins of the ECM • Each collagen molecule is a triple helix consisting of • three entwined a chains Glycine HYP P

  13. Collagen Structure (膠原蛋白的結構) tropocollagen

  14. Collagen Structure

  15. Some types of collagen and their properties (軟骨)

  16. Fibrous proteins - Elastin 彈力蛋白 • Elastin gives tissues their elasticity • Highly hydrophobic protein • - Rich in proline and glycine Hydrophobic peptide Crosslink peptide

  17. Fibrous proteins - Fibronectin 纖維結合素 Arg-Gly-Asp (RGD) sequence： - Specific for recognition by cell-surface receptor (major integrin) - In fibronectin and laminin are important FIG. 3(C) - p.264

  18. Fibrous proteins - Laminin 層黏連結蛋白 Each of polypeptide ＞ 1500 a.a α chain β chain γ chain Fig. 3(D) - p.264

  19. A Current Model of the Molecular Structure of a Basal Lamina 珍珠素(perlecan)即屬於硫酸肝素蛋白多醣(heparan sulfate proteoglycan, HSPG)的一種

  20. Degrade all kinds of extracellular matrix– Matrix metalloproteinases (MMPs) ♣ Zinc-dependent endopeptidases 2 Cysteine 半胱胺酸 有四種endopeptidases：絲氨酸(serine)蛋白酶、胱氨酸(cystine)蛋白酶、 天門冬氨酸(aspartyl)蛋白酶，基質金屬蛋白酶，四種都和上述腫瘤發生、傳移過程有關。MMPs是腫瘤發生過程中四種蛋白質水解酶(proteases)最重要的一種 基質金屬蛋白酶(Matrix metalloproteinases, MMPs) 是可分解細胞外基質(extracellular matrix, ECM) 蛋白的酵素，不管在正常或有病的細胞中，他們都扮演重要的角色。蛋白質水解酶(proteases)在許多疾病中扮演重要的角色，細胞外蛋白質水解酶是腫瘤細胞穿過組織細胞所須的物質，水解ECM蛋白對侵掠性腫瘤的轉移(metastasis)是必須的; 此外,，支援腫瘤生長的血管增生也借著侵略表皮細胞來水解ECM蛋白。 ☻ singal peptide ☻ propeptide☻ catalytic domain ☻ hinge region☻ haemopexin domain ♣ Five main regions: http://journals.cambridge.org/fulltext_content/ERM/ERM5_23/S1462399403006628sup017.gif

  21. An overview of the extracellular matrix http://nihroadmap.nih.gov/.../Dustin_ExecSumm2007.asp

  22. Kyle R. Legate, Eloi Montañez, Oliver Kudlacek and Reinhard Füssler, ILK, PINCH and parvin: the tIPP of integrin signalling, Nature Reviews Molecular Cell Biology, 7(2006)20-31.

  23. Integrin(整合素) ♦跨膜的異二聚體(heterodimers)，以α及β兩種次單位以非共價鍵的方式所組成 ♦ 目前至少有22種不同的I整合素 被發現，約有16種的α次單元及8種β次單元相互配對組合而成。 ♦ 與配位體結合要二價離子(Ca2+ )參與 β-次單元 α-次單元 I-區域 似I-區域 七葉β-螺旋體 細胞膜 http://www.e-stork.com.tw/picture/20050610_02.jpg http://www.baibio.com/wiki/images/thumb/f/f3/%E6%95%B4%E8%81%94%E8%9B%8B%E7%99%BD.jpg/180px-%E6%95%B4%E8%81%94%E8%9B%8B%E7%99%BD.jpg

  24. 219.221.200.61/ywwy/zbsw(E)/edetail4.htm

  25. 細胞死亡 • 壞死(necrosis): 細胞受到化學因素(如強酸強鹼、有毒物質) 、物理因素(如熱、輻射)和生物因素(如病原體)等環境因素的傷害，引起細胞死亡的現象。 • 計畫性的細胞死亡(apoptosis): 又稱作程序性細胞死亡，細胞受環境刺激後，在基因調控之下所產生的自然死亡現象。

  26. Necrosis （細胞壞死） • 初期細胞外形呈不規則狀，細胞膜的通透性增加，內質網擴張和染色質不規則移位，接著細胞內細胞核腫脹、溶小體破裂使具分解作用的酵素流出。最後細胞膜破裂、細胞內粒線體漲破和染色質流失，破壞整個細胞結構使細胞死亡。 web1.nsc.gov.tw/ctpda.aspx?xItem=11207&ctNode...

  27. Apoptosis （細胞計畫性死亡，凋亡） http://www.microbiologybytes.com/virology/kalmakoff/baculo/pics/Apoptosis.gif

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  29. Thanks for your attention

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