- 學位論文
微量礦物元素硒、鋅、維生素A、維生素C及維生素E保護皮膚角質細胞抵抗中波長紫外線傷害機制之探討
Study of mechanisms of selenium, zinc, vitamin A, vitamin C, and vitamin E, protect skin keratinocytes against UVB irradiation.
摘要
紫外線為一環境危險因子，長期暴露太陽紫外線中的UVB會引起皮膚造成發炎、老化、細胞死亡、誘發癌症發生等傷害。近年來由於臭氧層破壞，因此到達地表的紫外線輻射量增加，其中以UVB波段增加最多，UVB的增加將會對人體健康產生很大影響。角質細胞為皮膚表皮層中主要組成細胞，遭受到UVB的傷害機率也最大，因此保護角質細胞免於受到UVB的傷害十分重要。微量礦物元素硒、鋅、維生素A、維生素C及維生素E為維持人體健康所必需之營養物質，但其保護角質細胞免於受到紫外線傷害的機制尚未清楚。紫外線會導致細胞內產生大量的自由基，過量的自由基為引起老化及許多疾病之起因。我們研究發現硒、鋅、維生素A、維生素C及維生素E可有效防止UVB導致的抗氧化酵素轉錄作用抑制及活性氧物質產生。當角質細胞受到UVB照射時，會導致大量的促發炎因子，如腫瘤壞死因子、白介素- 6、白介素- 8的產生。但我們研究結果發現硒、鋅、維生素A、維生素C及維生素E處理之下，可明顯降低由UVB所誘導之促發炎因子mRNA的表現量。此外，細胞經硒、鋅、維生素A、維生素C、維生素E處理之下，可明顯抑制POMC的基因轉錄，從而抑制其衍生物α-MSH的表現，而達到抑制黑色素之生成，且經由老化指標β -半乳糖苷酶活性分析、基質金屬蛋白酶（matrix metalloproteinases，MMPs）和其轉錄因子activating protein-1（AP-1）組成分子c-Jun之表現分析，證實硒、鋅、維生素A、維生素C及維生素E可透過抑制UVB誘導之c-Jun表現，進而降低MMP-1、MMP-3和MMP-9基因轉錄作用，以防止UVB所導致的老化情形發生。再者，硒、鋅、維生素A、維生素C及維生素E處理之下，可有效防止角質細胞因UVB照射而導致的DNA 斷片化，減少停留在sub - G1的細胞數目，及防止粒線體膜電位下降等細胞凋亡的情形發生。更進一步研究發現，硒、鋅及維生素A、維生素C及維生素E可透過抑制死亡受體Fas及其信號連接蛋白Fas-associated protein with death domain （FADD）的表現，且使抗細胞凋亡蛋白Bcl-xL不受UVB影響，並降低pro-caspase 9及pro-caspase 3的活化，來避免角質細胞受到UVB的傷害而走向細胞凋亡。由以上結果可知，微量礦物元素硒、鋅、維生素A、維生素C及維生素E可發揮其抗氧化功能，降低UVB誘導的發炎反應及老化情形，亦可避免角質細胞經由死亡受體途徑及粒線體途徑走向細胞凋亡，證實硒、鋅、維生素A、維生素C及維生素E具有保護皮膚角質細胞免於受到UVB傷害之功效。
並列摘要
Ultraviolet radiation is an important environmental risk factor of cell death and skin ageing. Dietary trace minerals (such as selenium, zinc) and vitamins (such as vitamin A, C, and vitamin E) have been shown to be anti-oxidative; however, it is not known whether they are against the UVB-induced damages or not. This study was designed to investigate the effects of selenium (Se), zinc (Zn), vitamin A, vitamin C, and vitamin E on UVB-induced damages in the human keratinocyte cell line HaCaT. Results showed Se, Zn, vitamin A, vitamin C, and vitamin E treatments significantly reduced the formation of sunburn cells. In addition, the decreases in mRNA expressions of antioxidant enzymes including SOD 1, catalase, GPX were prevented. Besides, UVB-induced reactive oxygen species （ROS） levels and pro-inflammation cytokines including tumor necrosis factor-α （TNF-α）, interleukin-6 （IL-6）, and interleukin-8（IL-8） were reduced. Moreover, Zn and Se treatments significantly inhibited POMC mRNA expression to avoid the UVB-induced skin pigmentation. Se, Zn, vitamin A, vitamin C, and vitamin E treatments also significantly reduced the formation of β-galactosidase-positive cells, being a aging marker, induced by UVB; meanwhile, these treatments inhibited matrix metalloproteinases（MMP-1, MMP-3, and MMP-9） transcription through reducing c-Jun of activator protein-1（AP-1）member expression. The UVB-induced DNA fragmentation and sub-G1 phase cells arrest were decreased by treatments of Se, Zn, vitamin A, vitamin C, and vitamin E. In accordance with these findings, the anti-apoptotic protein Bcl-xL expression was reduced; the loss of mitochondrial membrane potential （Δψm）and cleavage of pro-caspase 9, pro-caspase 3 were inhibited. Besides, the expression of death receptor（Fas）and Fas-associating protein with death domain（FADD）were eliminated. Conclusively, Se, Zn, vitamin A, vitamin C, and vitamin E treatments would effectively prevent keratinocytes from UVB-induced damages through reducing production of ROS and pro-inflammation cytokines as well as expressions of POMC, and MMPs resulting in avoiding mitochondrial dysfunction and inactivating death receptor pathway to escape from UVB-induced aging and apoptosis.
參考文獻
被引用紀錄
延伸閱讀
- 楊榮森（2019）。紫外線指數、維生素D3與骨骼保健。健康世界，(509)，7-8。https://www.airitilibrary.com/Article/Detail?DocID=16077059-201905-201906100004-201906100004-7-8
- 李榕榕、簡治伸、成和正、洪偉欽（2007）。運動員口服維他命C與膠原蛋白對曬後皮膚油脂與彈性之修復成效研究。載於臺灣運動生理暨體能學會（主編），國際運動生理與體能領域學術研討會（頁82-82）。臺灣運動生理暨體能學會。https://doi.org/10.29835/TSEPFANNUAL.200705.0082
- Sheu, S. J., & Wu, T. T. (2009). 葡萄紅素可經由大傳導鈣活化性鉀離子通道保護人類視網膜色素上皮細胞對抗紫外線之傷害. The Kaohsiung Journal of Medical Sciences, 25(7), 381-388. https://www.airitilibrary.com/Article/Detail?DocID=1607551X-200907-200907170052-200907170052-381-388
- 彭瓊琿、石瑩、彭耀寰（1998）。The Photochemical Mechamism and the Versatile Functions of the Superfine Solid Metal Oxide Additives in Sunscreen Cosmetics.。弘光學報，(31)，139-151。https://doi.org/10.6615/HAR.199804.31.06
- 陳尚球、朱希斌、李延康（1957）。Studies on the Intake, Blood Level and Urinary Excretion of Vitamin A, Carotene, Thiamine, Riboflavin and Ascorbic acid in Chinese Men. IV. Studies on the Dietary Intake, Blood Level and Urinary Excretion of Riboflavin.。化學，(46年2)，79-89。https://doi.org/10.6623/chem.1957009