建立鎘活化切絲蛋白的訊號途徑

中文摘要鎘為生物體非必需的元素，當被生物體過量攝取，則會對生物體造成嚴重的毒害。先前的研究指出鎘會影響細胞骨架的聚合作用。由於細胞骨架上肌動蛋白絲的聚合也受切絲蛋白的影響。本研究重點在於探討鎘對於人類胚胎腎臟細胞HEK293切絲蛋白活性的影響，及其參與的訊號傳遞系統。在我們的研究發現HEK293細胞處理鎘後切絲蛋白活性的上升以及PTEN蛋白表現量的下降。PTEN在細胞內主要功能為負調控PI3K訊號傳遞途徑。因此我們觀察鎘是否藉由PTEN/PI3K路徑進而影響切絲蛋白活性。我們對細胞施加PI3K的抑制劑LY294002，同樣會觀察到切絲蛋白的活性也因抑制了PI3K而受到阻斷。在細胞中表現PTEN則可降低切絲蛋白的活性。分析PTEN下游因子發現PI3K會透過下游Rho-GTPase以及PKD影響切絲蛋白活性。本研究將建立鎘對於切絲蛋白的訊號傳遞路徑。

關鍵字

切絲蛋白；肌動蛋白；肌動蛋白單體；肌動蛋白鏈；肌動蛋白絲；鈣離子載體；踏車循環；層狀偽足；收縮環；磷酸化；聚合作用；去聚合作用

並列摘要

英文摘要 Cadmium is a non-essential trace element for plant or animal life, excessive intake may cause severe poisoning to organisms. Previous studies indicated that cadmium affects the polymerization of the cytoskeleton. Because the polymerization of actin filaments is affected by cofilins activity. We focused in this study the effects of cadmium on cofilin activity and the involved signaling pathway in Hek293 cells. We found that cadmium treatment increased cofilin activity and decreased PTEN protein level in HEK293 cells. PTEN is a widely known negative regulator of PI3K pathway. Investigated whether cadmium regulates cofilin activity through PTEN/PI3K pathway. .Addition of PI3K inhibitor (LY294002) also blocked the cadmium-induced cofilin activation. We found that overexpression of PTEN decreased cofilin activity. PI3K and its downstream effectors, including Rho-GTPase and PKD also modulate cofilin activity. Our results established the signal transduction pathway for cadmium-induced cofilin activation.

並列關鍵字

Cofilin ； Actin ； G-actin ； F-actin ； Actin filament ； Calcium ionophore ； Treadmilling cycle ； Lamellipodia ； Contractile rings ； Phosphorylation ； Polymerization ； Depolymerization

參考文獻

Aghajanian A, Wittchen ES, Campbell SL, Burridge K (2009) Direct activation of RhoA by reactive oxygen species requires a redox-sensitive motif. PloS one 4: e8045

Aizawa H, Sutoh K, Yahara I (1996) Overexpression of cofilin stimulates bundling of actin filaments, membrane ruffling, and cell movement in Dictyostelium. The Journal of cell biology 132: 335-344

Allwood EG, Smertenko AP, Hussey PJ (2001) Phosphorylation of plant actin-depolymerising factor by calmodulin-like domain protein kinase. FEBS letters 499: 97-100

Ambach A, Saunus J, Konstandin M, Wesselborg S, Meuer SC, Samstag Y (2000) The serine phosphatases PP1 and PP2A associate with and activate the actin-binding protein cofilin in human T lymphocytes. European journal of immunology 30: 3422-3431

Ashworth S, Teng B, Kaufeld J, Miller E, Tossidou I, Englert C, Bollig F, Staggs L, Roberts IS, Park JK, Haller H, Schiffer M (2010) Cofilin-1 inactivation leads to proteinuria--studies in zebrafish, mice and humans. PloS one 5: e12626

國際替代計量

建立鎘活化切絲蛋白的訊號途徑

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