藻青素調節MAPK途徑抑制B16F10黑色素形成之探討

Melanogenesis Inhibitory effects of CPC regulation of MAPK pathway

翁于婷(Yu-Ting Weng)

指導教授 ： 吳立真

國立暨南國際大學/科技學院/生物醫學科技研究所/碩士(2008年)

摘要

大多數皮膚病變的特徵是由於黑生素生成增多，包括色素沉著過度的狀態，例如，黑斑、黑皮病和雀斑。酪胺酸酶 ( tyrosinase )為黑色素生合成過程中速率決定酵素1，酪胺酸酶的表現需要經由一連串的訊息傳遞調控，黑色素生合成之訊息傳遞並未完全確認，然而，許多研究已證實，cAMP 在黑色素生合成調控上扮演重要角色，首先經由PKA 活化 CREB ( cAMP responsive element binding protein ) 可調控 tyrosinase 的轉錄因子 - MITF ( microphthalmia associated transcription factor )轉錄活性。其次， cAMP經由活化 ERK而使 MITF 水解，因此，可降低酪胺酸酶表現。第三， cAMP可經由抑制 phosphatidylinositol 3-kinase ( PI3K ) 之 活 化，抑 制 protein kinase B ( Akt ) 表 現，促 進 MITF 的表現，增加酪胺酸酶的表現。
黑色素生合成須經由一連串氧化反應步驟形成，而許多美白有效成分具有抗氧化能力，如維生素C，為還原劑，可將黑色素生合成步驟中的中間產物還原，減緩黑色素生合成。藻青素 ( c-phycocyanin ; CPC ) 為藍綠藻主要成分之一，研究指出c-phycocyanin 具有抗氧化與清除自由基的特性。因此，我們研究 c-phycocyanin 是否影響黑色素生合成以及其分子機制。由實驗得知，c-phycocyanin 經由活化 MAPK/ERK途徑來導致 MITF 蛋白質表現下降，降低酪胺酸酶活性與抑制黑色素生成。另外，c-phycocyanin 會增加 cAMP 表現量與 PKA 活性。此外，結果顯示c-phycocyanin 會進入細胞核影響 PKA 磷酸化下游分子，進而達到抑制黑色素形成。

關鍵字

藻青素 ； 黑色素生合成 ； 黑色素 ； 酪胺酸酶

並列摘要

An increased level of melanin is one of the characteristics of several skin diseases, including acquired hyperpigmentation such as melasma, postinflammatory melanoderma, and solar lentigo. Tyrosinase catalyzes the rate-limiting reaction of melanogenesis. The formation of melanin is regulated by the activity or the expression of the enzyme. Although the whole picture of the signal transduction involved in melanogenesis remains unclear, it is suggested that cAMP plays an important role in the biosynthesis. cAMP modulates melanogenesis in three aspects. Firstly, cAMP regulates the activation of protein kinase A, which phosphoylates the transcription protein, CREB. Phosphoryed CREB further facilitates the expression of microphthalmia associated transcription factor (MITF), which is the transcription factor of tyrosinase. Secondly, cAMP induces MITF degradation through the activation of ERK, and therefore, down-regulates the expression of tyrosinase. Thirdly, cAMP inhibits the activation of phosphatidylinositol 3-kinase (PI3K), which results in the repression of protein kinase B (Akt) expression, yet up-regulates MITF.
Melanogenesis involves a series of redox reactions. Antioxidants such as ascorbic acid, retard melanogenesis through reduction of oxidized intermediates. C-phycocyanin (CPC), a component of blue green algae, has been studied to have anti-oxidative capacity and free radical scavenging activity. In the present study, the results showed that B16F10 melanin content and tyrosinase expression were reduced by the addition of CPC. In addition, CPC increased cAMP level and protein kinase A (PKA) activity. CPC were uptaken and trapped in cell nuclei to inhibit melanogenesis possibly the through suppression of the PKA pathway.

並列關鍵字

c-phycocyanin ； melanogenesis ； melanin ； tyrosinase

參考文獻

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