Adaptations of neurotransmitter synthesis to chronic hypoxia in cell culture.
Adaptations of neurotransmitter synthesis to chronic hypoxia in cell culture.
复制标题
神经递质合成对细胞培养中慢性缺氧的适应。
DOI：
10.1016/0167-4889(87)90085-1
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Raybin,DM
中科院分区：
文献类型：
--
作者：
Feinsilver,SH;Wong,R;Raybin,DM
酪氨酸羟化酶和色氨酸羟化酶被广泛认为分别是儿茶酚胺和5-羟色胺合成的限速酶。这两种酶都需要氧气，动力学特性表明氧气的可用性可能会限制大脑中这些神经递质的合成。使用嗜铬细胞瘤细胞作为儿茶酚胺合成的细胞培养模型，和神经母细胞瘤细胞作为5-羟色胺合成的模型，在控制和缺氧条件下测量酶活性。酪氨酸羟化酶和色氨酸羟化酶的活性大幅增加慢性接触，但不是与急性接触。在酪氨酸羟化酶的情况下，增加的酶含量与缺氧的帐户增加的活动。这表明慢性缺氧维持神经递质合成的机制。细胞内代谢物的测量显示，多巴胺或去甲肾上腺素在缺氧嗜铬细胞瘤细胞中没有变化，与一个简单的适应机制一致。然而，在神经母细胞瘤细胞中，缺氧与5-羟色胺浓度的增加有关。其原因尚不清楚。
Tyrosine hydroxylase and tryptophan hydroxylase are widely held to be rate-limiting for the synthesis of the catecholamines and serotonin, respectively. Both enzymes are oxygen-requiring and kinetic properties suggest that oxygen availability may limit synthesis of these neurotransmitters in the brain. Using pheochromocytoma cells as a cell culture model for catecholamine synthesis, and neuroblastoma cells as a model for serotonin synthesis, enzyme activity was measured under control and hypoxic conditions. Both tyrosine hydroxylase and tryptophan hydroxylase activity increased substantially with chronic exposure but not with acute exposure. In the case of tyrosine hydroxylase, increased enzyme content with hypoxia accounts for increased activity. This suggests a mechanism for the maintenance of neurotransmitter synthesis with chronic hypoxia. Measurement of intracellular metabolites revealed no change in dopamine or norepinephrine in hypoxic pheochromocytoma cells, consistent with a simple adaptive mechanism. However, in neuroblastoma cells, hypoxia was associated with an increase in serotonin concentration. The reasons for this are still unclear.