Arsenic trioxide (As2O3) has been used clinically for treating cancers by inducing apoptosis of cancer cells. The molecular mechanisms and its targets for As2Os to induce apoptosis remain elusive. Here, we investigate...Arsenic trioxide (As2O3) has been used clinically for treating cancers by inducing apoptosis of cancer cells. The molecular mechanisms and its targets for As2Os to induce apoptosis remain elusive. Here, we investigated the molecular mechanisms underlying mitochondrial apoptosis induced by As2O3. Exposure of isolated mouse liver mitochondria with As2Oa elicited permeability transition pore (PTP) opening, cytochrome c (cyt c) release (CCR) and collapse of mitochondrial membrane potential (△(?)m). PTP inhibitors cyclosporin A (CsA), Bongkrekic acid (BA) and Bcl-XL prevented these mitochondrial apoptosis and CCR induced by As2C】3. We, for the first time, provided evidence suggesting that As2O3 induces mi-展开更多
PUMA(p53 up-regulated modulator of apoptosis)是近年发现的可被内外源性p53快速诱导、具有强大促凋亡作用的Bcl-2蛋白家族一员。它通过BH3结构域与其他Bcl-2家族蛋白相互作用,诱导细胞色素c释放,引起凋亡。PUMA引起的凋亡有两种(p53...PUMA(p53 up-regulated modulator of apoptosis)是近年发现的可被内外源性p53快速诱导、具有强大促凋亡作用的Bcl-2蛋白家族一员。它通过BH3结构域与其他Bcl-2家族蛋白相互作用,诱导细胞色素c释放,引起凋亡。PUMA引起的凋亡有两种(p53依赖的和p53不依赖的)调控通路,已有研究表明PUMA敲除可显著抑制细胞凋亡。对于该基因的调控机制、作用机制及在肿瘤治疗中的应用等方面的问题,正待深入研究。展开更多
文摘Arsenic trioxide (As2O3) has been used clinically for treating cancers by inducing apoptosis of cancer cells. The molecular mechanisms and its targets for As2Os to induce apoptosis remain elusive. Here, we investigated the molecular mechanisms underlying mitochondrial apoptosis induced by As2O3. Exposure of isolated mouse liver mitochondria with As2Oa elicited permeability transition pore (PTP) opening, cytochrome c (cyt c) release (CCR) and collapse of mitochondrial membrane potential (△(?)m). PTP inhibitors cyclosporin A (CsA), Bongkrekic acid (BA) and Bcl-XL prevented these mitochondrial apoptosis and CCR induced by As2C】3. We, for the first time, provided evidence suggesting that As2O3 induces mi-
文摘PUMA(p53 up-regulated modulator of apoptosis)是近年发现的可被内外源性p53快速诱导、具有强大促凋亡作用的Bcl-2蛋白家族一员。它通过BH3结构域与其他Bcl-2家族蛋白相互作用,诱导细胞色素c释放,引起凋亡。PUMA引起的凋亡有两种(p53依赖的和p53不依赖的)调控通路,已有研究表明PUMA敲除可显著抑制细胞凋亡。对于该基因的调控机制、作用机制及在肿瘤治疗中的应用等方面的问题,正待深入研究。
