Differential effects of specific amino acid restriction on glucose metabolism, reduction/oxidation status and mitochondrial damage in DU145 and PC3 prostate cancer cells.

Differential effects of specific amino acid restriction on glucose metabolism, reduction/oxidation status and mitochondrial damage in DU145 and PC3 prostate cancer cells.
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DOI:
10.3892/ol.2011.237
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发表时间:
2011-01-18
期刊:
影响因子:
2.9
通讯作者:
Meadows GG
Meadows GG
中科院分区:
医学4区
文献类型:
--
作者:
Liu X;Fu YM;Meadows GG

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选择性氨基酸限制靶向线粒体诱导DU 145和PC 3前列腺癌细胞凋亡利用生化分析和流式细胞术分析葡萄糖消耗、乳酸产生、丙酮酸脱氢酶(PDH)、烟酰胺腺嘌呤二核苷酸(NAD)/NADH和烟酰胺腺嘌呤二核苷酸磷酸(NADP)/NADPH比率、线粒体谷胱甘肽过氧化物酶(GPx)、锰超氧化物歧化酶(SOD)、谷胱甘肽、在各种氨基酸剥夺条件下培养的DU 145和PC前列腺癌细胞中的活性氧(ROS)和DNA损伤。限制酪氨酸和苯丙氨酸(Tyr/Phe),谷氨酰胺(Gln)或甲硫氨酸(Met)差异调节葡萄糖代谢和PDH和抗氧化酶活性的线粒体中的两个前列腺癌细胞系。在DU 145细胞中,Gln和Met限制增加葡萄糖消耗和减少乳酸产生,但Tyr/Phe限制没有。所检查的限制增加线粒体PDH活性和ROS积累。Gln和Met限制增加GPx活性。Tyr/Phe和Met限制在限制的前2天增加SOD,并且活性在第4天恢复到基础水平。所有氨基酸限制降低还原型谷胱甘肽(GSH),并诱导线粒体DNA损伤。在PC 3细胞中,所有氨基酸限制减少葡萄糖消耗和乳酸产生。Gln限制增加ROS和升高GPx活性。Tyr/Phe限制增加SOD活性。氨基酸限制降低GSH,但不引起线粒体DNA损伤。特定氨基酸依赖性差异调节DU 145和PC 3前列腺癌细胞系中的葡萄糖代谢、线粒体氧化还原反应和线粒体损伤。
Selective amino acid restriction targets mitochondria to induce apoptosis of DU145 and PC3 prostate cancer cells. Biochemical assays and flow cytometry were uitilized to analyze the glucose consumption, lactate production, pyruvate dehydrogenase (PDH), nicotinamide adenine dinucleotide (NAD)/NADH and nicotinamide adenine dinucleotide phosphate (NADP)/NADPH ratios, mitochondrial glutathione peroxidase (GPx), manganese superoxide dismutase (SOD), glutathione, reactive oxygen species (ROS) and DNA damage in DU145 and PC prostate cancer cells cultured under various amino acid deprived conditions. Restriction of tyrosine and phenylalanine (Tyr/Phe), glutamine (Gln) or methionine (Met) differentially modulated glucose metabolism and PDH and antioxidant enzyme activity in the mitochondria of the two prostate cancer cell lines. In DU145 cells, Gln and Met restriction increased glucose consumption and decreased lactate production, but Tyr/Phe restriction did not. The examined restrictions increased mitochondrial PDH activity and accumulation of ROS. Gln and Met restriction increased GPx activity. Tyr/Phe and Met restriction increased SOD during the first 2 days of the restriction, and the activity returned to the basal level on day 4. All amino acid restrictions decreased reduced glutathione (GSH) and induced mitochondrial DNA damage. In PC3 cells, all amino acid restrictions reduced glucose consumption and lactate production. Gln restriction increased ROS and elevated GPx activity. Tyr/Phe restriction increased SOD activity. The amino acid restriction decreased GSH, but did not cause mitochondrial DNA damage. Specific amino acid dependency differentially regulates glucose metabolism, oxidation-reduction reactions of mitochondria and mitochondrial damage in DU145 and PC3 prostate cancer cell lines.
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