Clarifying the role of phosphodiesterase in resveratrol mediated mitochondrial dynamics in senescent yeast cells

探究磷酸二酯酶在白藜蘆醇對酵母菌衰老細胞的粒線體調控的機制中所扮演的角色

張文涓(Chang, Wen Chuan)

指導教授 ： 張壯榮

國立清華大學/生命科學院/生物科技研究所/碩士(2016年)

摘要

粒線體在細胞中扮演很重要的角色，特別是在能量調控上。藉由粒線體分裂和融合的過程可以幫助粒線體維持正常的功能。失去功能的粒腺體可能跟老化的過程有關，並且在衰老的細胞中可以發現比較多碎裂型態的粒線體。白藜蘆醇是一種天然的多酚抗氧化物，根據我們實驗室的研究結果，白藜蘆醇可以減少碎裂型態的粒線體並且降低衰老細胞中活性氧化物的含量。然而白藜蘆醇的作用機制仍然在研究領域中有不同的爭辯。我們實驗室過去發現缺乏磷酸二酯酶後會抑制住白藜蘆醇對衰老的酵母菌細胞的效果，因此我們想進一步去探討磷酸二酯酶在白藜蘆醇對粒線體動態平衡的調控所扮演的角色。在我們的研究結果中發現將磷酸二酯酶過度表現會影響白藜蘆醇調控粒線體的型態，但卻不會影響白藜蘆醇降低活性氧化物的機制。與缺乏磷酸二酯酶的結果比較後，我們可以推論出白藜蘆醇在調控衰老酵母菌細胞中的粒腺體型態及降低活性氧化物的過程中是需要磷酸二酯酶來作用的。這些結果提供更多資訊讓我們了解白藜蘆醇在細胞中的作用機轉。

關鍵字

粒線體動態平衡 ； 衰老 ； 白藜蘆醇 ； 磷酸二酯酶

並列摘要

Mitochondria play critical roles in cells, especially in energy homeostasis. One way to regulate mitochondrial homeostasis and quality is via dynamic fission and fusion processes. Mitochondrial dysfunction may associate with aging process. Fragmentation of mitochondria was found in senescent cells. In addition, Resveratrol, one of the ROS scavengers, can reduce the ratio of the senescent yeast cells with fragmented mitochondria. Studies indicated that resveratrol inhibits the activity of phosphodiesterase to ameliorate the aging phenotype in mammalian cells. Whether resveratrol affects cellular activity through phosphodiesterase is still under extensive debate. Our previous results suggested that inhibiting phosphodiesterase compromise the effects of resveratrol in senescent yeast cells. We aim to elucidate the role of phosphodiesterase in the mechanism of resveratrol mediated-mitochondrial dynamics in senescent cells. The results showed overexpression of PDE2 affects resveratrol to reduce the ratio of senescent cells with fragmented mitochondria, but not interfere resveratrol to mediate superoxide removal. Comparing to the wild type and Δpde2 cells, PDE2 is required for the effect of resveratrol on mitochondrial dynamics in senescent yeast cells. The results provide more understanding of underlying mechanisms of how resveratrol acts in senescent yeast cells.

並列關鍵字

Mitochondrial dynamics ； Senescent ； Resveratrol ； Phosphodiesterase

參考文獻

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