Enhanced oxidative stress and accelerated cellular senescence in glucose-6-phosphate dehydrogenase (G6PD)deficient human fibroblasts
Enhanced oxidative stress and accelerated cellular senescence in glucose-6-phosphate dehydrogenase (G6PD)deficient human fibroblasts
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DOI：
10.1016/s0891-5849(00)00331-2
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发表时间：
2000-07-15
影响因子：
7.4
通讯作者：
Chiu, DTY
中科院分区：
文献类型：
--
作者：
Ho, HY;Cheng, ML;Chiu, DTY
6-磷酸葡萄糖脱氢酶 (G6PD) 参与还原型烟酰胺腺嘌呤二核苷酸磷酸 (NADPH) 的生成和细胞氧化还原平衡的维持。使用 G6PD 缺陷的人包皮成纤维细胞 (HFF) 研究了有核细胞中 G6PD 缺陷的生物学效应。与正常 HFF 相比，G6PD 缺陷细胞的倍增 Lime 很容易从群体倍增水平 (PDL) 15 增加到 63。这伴随着 G(1) 细胞百分比的显着增加。在这些细胞早期进入不分裂状态（让人想起细胞衰老）之前，生长速度会减慢。这些细胞的衰老相关β-半乳糖苷酶（SA-β-gal）染色水平显着增加。 G6PD 活性在细胞生长中的重要性得到了以下发现的证实：缺陷细胞中活性 G6PD 的异位表达可防止其生长迟缓和早衰。从机制上讲，二氯荧光素 (H2DCF) 染色的 G6PD 缺陷细胞中荧光增强表明活性氧可能参与衰老。综上所述，我们的结果表明，G6PD 缺乏会使人成纤维细胞生长迟缓并加速细胞衰老。此外，G6PD 缺陷的 HFF 提供了一个有用的模型系统，用于描述氧化还原改变对细胞过程的影响。 (C) 2000 爱思唯尔科学公司。
Glucose-6-phosphate dehydrogenase (G6PD) is involved in the generation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) and the maintenance of the cellular redox balance. The biological effects of G6PD deficiency in nucleated cells were studied using G6PD-deficient human foreskin fibroblasts (HFF). in contrast to that of normal HFF, the doubling Lime of G6PD-deficient cells increased readily from population doubling level (PDL) 15 to 63. This was accompanied by a significant increase in the percentage of G(1) cells. The slow-down in growth preceded an early entry of these cells into a nondividing state reminiscent of cellular senescence. These cells exhibited a significant increase in level of senescence-associated beta-galactosidase (SA-beta-gal) staining. The importance of G6PD activity in cell growth was corroborated by the finding that ectopic expression of active G6PD in the deficient cells prevented their growth retardation and early onset of senescence. Mechanistically, the enhanced fluorescence in dichlorofluorescin (H2DCF)-stained G6PD-deficient cells suggests the possible involvement of reactive oxygen species in senescence. Taken together, our results show that G6PD deficiency predisposes human fibroblasts to retarded growth and accelerated cellular senescence. Moreover, G6PD-deficient HFF provides a useful model system for delineating the effects of redox alterations on cellular processes. (C) 2000 Elsevier Science Inc.