高良薑素對人類纖維真皮母細胞經UVB照射後粒線體動態平衡的保護作用

The effects of Galangin on mitochondrial dynamics following UVB exposure in human dermal fibroblast

程詩涵(Shih-Han Cheng)

指導教授 ： 謝錦源

共同指導教授 ： 蔡淦仁(Kan-Jen Tsai)

中山醫學大學/醫學科技學院/醫學檢驗暨生物技術學系/碩士(2022年)

https://doi.org/10.6834/csmu202200237

摘要

紫外線照射是導致皮膚老化的主要因素之一，最終會導致DNA損傷、氧化壓力及粒線體功能喪失。粒線體是不斷融合和分裂的動態胞器，粒線體的動態平衡會導致其形態的改變。先前的研究表示UVB照射會誘導粒線體分裂和抑制融合，進而損害粒線體形態。高良薑素是一種具有抗發炎和抗氧化的天然黃酮醇。然而高良薑素通過 UVB 誘導的線粒體功能障礙對皮膚真皮纖維母細胞的保護作用仍然未知。因此在這次研究中，我們研究高良薑素如何在UVB照射的情況下調節皮膚真皮纖維母細胞中的粒線體功能。我們的研究結果表示，高良薑素增加粒線體融合相關蛋白如OPA-1並抑制分裂相關蛋白如Drp-1和Fis-1；促凋亡蛋白如細胞色素c、Bak和Bax，在UVB照射下恢復粒線體功能。此外，在高良薑素處理後，碎片化的粒線體會被逆轉。值得注意的是，Drp1、Bak、Bax和Cofilin1的粒線體易位在高良薑素處理組中會被減弱，表示對粒線體的保護作用。此外，透過Mdivi-1和小干擾RNA（siRNA）對Drp1進行失活和抑制，進一步證明在UVB誘導的損傷模型中粒線體功能的恢復。此外，利用免疫共沉澱法證明Cofilin和Drp1的相互作用會促進粒線體易位。總之，我們的研究結果表示高良薑素可以預防由UVB誘導的粒線體功能障礙引起的細胞凋亡。我們的研究結果表示高良薑素具有發展化妝品補充劑的潛力。

關鍵字

高良薑素 ； 粒線體的動態平衡 ； 人類皮膚真皮纖維細胞

並列摘要

UV irradiation is one of the major factor that cause skin aging, which ultimately leads to DNA damage, oxidative stress, and mitochondrial dysfunction. Mitochondria are dynamic organelles that continuously fusion and fission, and the dynamic balance of mitochondria will lead to changes in their morphology. Previous studies demonstrated that UVB irradiation induced mitochondrial fission and inhibited fusion, thereby impairing mitochondrial morphology. Galangin is a natural flavonol with possesses anti-inflammatory and anti-oxidative properties. However, the cytoprotective effects of galangin in skin dermal fibroblasts through UVB-induced mitochondrial dysfunction is still unknown. Therefore, in this study, we investigated how galangin modulates the mitochondria functions in skin dermal fibroblasts under UVB irradiation. Our results indicated that galangin increased mitochondrial fusion-related proteins such as OPA-1 and inhibited fission-related proteins such as Drp-1, Fis-1; as well as pro-apoptotic proteins such as cytochrome c, Bak and Bax, thereby restoring mitochondrial function under UVB exposure. Furthermore, fragmented mitochondria were reversed following galangin treatment. Notably, mitochondrial translocation of Drp-1, Bak, Bax, and Cofilin1 were attenuated in galangin treated groups indicating its mitochondrial protecting role. In addition, inactivation and inhibition of Drp1 through Mdivi-1 or small interfering RNAs (siRNA) further demonstrated the reviving of mitochondria function in UVB-induced damage model. Additionally, co-immunoprecipitation demonstrated the interaction of Cofilin1 with Drp1 to facilitate its mitochondria translocation. In conclusion, our findings suggest that galangin may prevent apoptosis caused by UVB-induced regulating mitochondrial dysfunction. Our findings showed that galangin has the potential to develop as supplements in cosmetic products.

並列關鍵字

Galangin ； mitochondrial dynamics ； human skin dermal fibroblast

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