熱休克透過活性氧物質經由粒線體與死亡受體途徑誘發角膜細胞凋亡

Heat shock induces apoptosis through reactive oxygen species involving mitochondrial and death receptor pathways in corneal cells

林憲忠(Hsien-Chung Lin)

指導教授 ： 郭柏麟

高雄醫學大學/醫學院/臨床醫學研究所/碩士(2011年)

摘要

雖然之前有許多的研究探討紫外光對眼睛的傷害，但紅外線對眼睛的分子效應則一無所知。紅外線會產生熱，而熱休克已被廣泛認定是一種環境壓力源。因此，本研究是首度探討熱效應對Statens Seruminstitut Rabbit 角膜細胞 (SIRC) 的生物效應。我們的研究顯示熱休克會經由誘發細胞凋亡進而抑制細胞增殖。 熱休克會讓 Bax/Bcl-2比例改變， caspase-9活性增加，引發粒線體凋亡途徑。此外，熱休克也會經由Fas ligand 的改變，使得caspase-8 活性增加，誘發死亡受體凋亡途徑。再者，我們也發現熱休克誘發細胞凋亡中，活性氧物質(ROS)的產生也是個關鍵的媒介。這實驗也顯示抗氧化劑維他命C可以顯著地降低熱休克誘發的細胞凋亡。 綜言之，在熱休克誘發的角膜細胞凋亡模式中， 活性氧物質扮演一個重要角色，且涉及死亡受體途徑與粒線體途徑.

關鍵字

熱休克 ； 角膜 ； 細胞凋亡 ； 活性氧物質 ； 粒線體

並列摘要

Although many studies have been performed to elucidate the molecular consequences of ultraviolet irradiation, little is known about the effect of infrared radiation on ocular disease. In addition to photons, heat is generated as a consequence of infrared irradiation, and heat shock is widely considered to be an environmental stressor. Here, we are the first to investigate the biological effect of heat shock on Statens Seruminstitut Rabbit Cornea (SIRC) cells. Our results indicate that heat shock exhibits effective cell proliferation inhibition by inducing apoptosis. Heat shock triggers the mitochondrial apoptotic pathway indicated by a change in Bax/Bcl-2 ratios, resulting in caspase-9 activity. In addition, heat shock triggered the death receptor apoptotic pathway indicated by a change in Fas ligand expression, resulting in caspase-8 activity. Furthermore, we also found that generation of reactive oxygen species (ROS) is a critical mediator in heat shock-induced apoptosis. In addition, the antioxidant vitamin C significantly decreased heat shock mediated apoptosis. Taken together, these findings suggest a critical role for ROS involving mitochondrial and death receptor pathways in heat shock-mediated apoptosis of cornea cells.

並列關鍵字

heat shock ； cornea ； apoptosis ； ROS ； mitochondria

參考文獻

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