METABOLISM VIA THE PENTOSE-PHOSPHATE PATHWAY IN RAT PHEOCHROMOCYTOMA PC12 CELLS - EFFECTS OF NERVE GROWTH-FACTOR AND 6-AMINONICOTINAMIDE

METABOLISM VIA THE PENTOSE-PHOSPHATE PATHWAY IN RAT PHEOCHROMOCYTOMA PC12 CELLS - EFFECTS OF NERVE GROWTH-FACTOR AND 6-AMINONICOTINAMIDE
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DOI:
10.1007/bf01000236
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发表时间:
1987-06-01
影响因子:
4.4
通讯作者:
KAUFFMAN, FC
KAUFFMAN, FC
中科院分区:
医学3区
文献类型:
--
作者:
DAVIS, LH;KAUFFMAN, FC

文献摘要

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将大鼠嗜铬细胞瘤 PC 12 细胞暴露于 0.1 mM 6-氨基烟酰胺 (6AN) 24 小时,导致 6-磷酸葡萄糖酸增加 500 倍,表明葡萄糖通过磷酸戊糖途径的氧化酶进行活跃代谢。通过用神经生长因子(NGF)(100 ng 7S/ml)处理细胞,24小时时在6AN处理的细胞中积累的6-磷酸葡萄糖酸的量显着增加,表明此时通过戊糖途径的葡萄糖代谢被NGF增强。这种通过戊糖途径对代谢的刺激可能是对 NGF 的晚期反应,因为 6AN 处理的细胞中 6-磷酸葡萄糖酸积累的初始速率在存在和不存在 NGF 的情况下是相同的。此外,在最初的六小时孵育期内,对照细胞和 NGF 处理细胞中 1-[14CO2]葡萄糖产生的 14CO2 量相同。 1-[14CO2]葡萄糖标记的磷酸己糖的比活性在对照细胞和 NGF 处理的细胞中也相同。 6AN 通过磷酸戊糖途径抑制代谢,但未能抑制 NGF 刺激的神经突生长,这表明 PC12 细胞中伴随 NGF 刺激的神经突生长的脂质生物合成所需的 NADPH 可以源自除戊糖磷酸途径的氧化酶以外的来源,或除了戊糖磷酸途径的氧化酶之外。
Exposure of rat phechromocytoma PC 12 cells to 0.1 mM 6-aminonicotinamide (6AN) for 24 hours resulted in a 500-fold increase in 6-phosphogluconate indicating active metabolism of glucose via the oxidative enzymes of the pentose phosphate pathway. Amounts of 6-phosphogluconate that accumulated in 6AN-treated cells at 24 hours were significantly increased by treatment of the cells with nerve growth factor (NGF) (100 ng 7S/ml) suggesting that metabolism of glucose via the pentose pathway at this time was enhanced by NGF. This stimulation of metabolism via the pentose pathway is probably a late response to NGF becasue initial rates of 6-phosphogluconate accumulation in 6AN-treated cells were the same in the presence and absence of NGF. Moreover, amounts of 14CO2 generated from 1-[14CO2]glucose during the initial six hour incubation period were the same in control and NGF-treated cells. Specific activities of hexose phosphates labeled from 1-[14CO2]glucose were also the same in control and NGF-treated cells. The observation that 6AN inhibited metabolism via the pentose phosphate pathway but failed to inhibit NGF-stimulated neurite outgrowth suggests that NADPH required for lipid biosynthesis accompanying NGF-stimulated neurite outgrowth from PC12 cells can be derived from sources other than, or in addition to, the oxidative enzymes of the pentose phosphate pathway.