Importance of glucose-6-phosphate dehydrogenase activity in cell death
Importance of glucose-6-phosphate dehydrogenase activity in cell death
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DOI：
10.1152/ajpcell.1999.276.5.c1121
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发表时间：
1999-05-01
影响因子：
5.5
通讯作者：
Stanton, RC
中科院分区：
文献类型：
--
作者：
Tian, WN;Braunstein, LD;Stanton, RC
细胞内氧化还原电位在细胞存活中起重要作用。主要的细胞内还原剂NADPH主要通过戊糖磷酸途径由限速酶葡萄糖-6-磷酸脱氢酶（G6 PDH）和6-磷酸葡萄糖酸脱氢酶产生。考虑到NADPH的重要性，我们假设G6 PDH在细胞死亡中起关键作用。结果表明：1）G6 PDH抑制剂增强H2 O2诱导的细胞死亡，2）G6 PDH过表达增强H2 O2诱导的细胞死亡抵抗力，3）血清剥夺（细胞死亡的刺激物）与G6 PDH活性降低相关，导致活性氧（ROS）升高;（4）向去血清细胞中加入G6 PDH底物几乎完全消除了去血清诱导的ROS升高; 5）G6 PDH抑制的结果包括细胞凋亡的显著增加、蛋白巯基的丢失和G6 PDH的降解;和6）G6 PDH抑制引起促分裂原活化蛋白激酶磷酸化的变化，这与用H2 O2观察到的变化相似。我们得出结论，G6 PDH通过影响氧化还原电位在细胞死亡中起着关键作用。
The intracellular redox potential plays an important role in cell survival. The principal intracellular reductant NADPH is mainly produced by the pentose phosphate pathway by glucose-6-phosphate dehydrogenase (G6PDH), the rate-limiting enzyme, and by 6-phosphogluconate dehydrogenase. Considering the importance of NADPH, we hypothesized that G6PDH plays a critical role in cell death. Our results show that 1) G6PDH inhibitors potentiated H2O2-induced cell death; 2) overexpression of G6PDH increased resistance to H2O2-induced cell death; 3) serum deprivation, a stimulator of cell death, was associated with decreased G6PDH activity and resulted in elevated reactive oxygen species (ROS); 4) additions of substrates for G6PDH to serum-deprived cells almost completely abrogated the serum deprivation-induced rise in ROS; 5) consequences of G6PDH inhibition included a significant increase in apoptosis, loss of protein thiols, and degradation of G6PDH; and 6) G6PDH inhibition caused changes in mitogen-activated protein kinase phosphorylation that were similar to the changes seen with H2O2. We conclude that G6PDH plays a critical role in cell death by affecting the redox potential.