| Summary: | 碩士 === 國立陽明大學 === 醫學生物技術暨檢驗學系暨研究所 === 99 === Protein deamidation that regulates a cellular response was first demonstrated in a study of Bcl-xL deamidation induced by DNA damage. Here, Bcl-xL is deamidated at Asn 52 and 66, where they are converted to Asp. Bcl-xL deamidation has been shown to inhibit its anti-apoptotic ability and leads to cell apoptosis. Cisplatin, a common anti- cancer drug, can cause cell death mediated by triggering DNA damage and reactive oxygen species (ROS). LY294002, a common PI3K/Akt inhibitor has been shown to synergize apoptosis in combination with Bcl-xL inhibitor in lung cancer cells.
In this study, we investigated the involvement of PI3K/Akt and ROS in Bcl-xL deamidation induced by cisplatin in A549 lung cancer cells. We observed when pre- treat the A549 cells with the glutathione inhibitor, buthionine-sulfoximine (BSO), cisplatin-induced Bcl-xL deamidation could be enhanced. This enhancement correlated with increasing ROS levels of the cells. We also showed that cell viability could be decreased by BSO treatment. In contrast, decreased ROS by using N-Acetyl-L-cystein (NAC) was detected that correlated with decreased Bcl-xL deamidation by cisplatin. We also observed that LY294002 combined with cisplatin could synergize ROS production and Bcl-xL deamidation. Similar results were evidenced by Akt1 knockdown or serum starvation experiments.
In summary, our data suggests that PI3K/Akt and ROS are involved in cisplatin-induced Bcl-xL deamidation in A549 lung cancer cells.
|
|---|
