Molecular mechanisms controlling nutritive blood flow: role of cytochrome P450 enzymes
Molecular mechanisms controlling nutritive blood flow: role of cytochrome P450 enzymes
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DOI：
10.1046/j.1365-201x.2000.00707.x
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发表时间：
2000-04-01
期刊：
影响因子：
--
通讯作者：
Gebremedhin, D
中科院分区：
文献类型：
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作者：
Harder, DR;Roman, RJ;Gebremedhin, D
这篇简短的综述总结了细胞色素 P450 (P450) 在调节脑组织和骨骼肌血流中的潜在作用。我们提供的数据表明，压力引起的大脑生肌活动在很大程度上负责 CBF 的自动调节。这种对压力的生肌反应部分是通过 P450 4A cDNA 编码的 P450 omega-羟化酶在动脉肌细胞中形成 20-HETE 来维持的。 CBF 的自动调节是脑循环的标志，尽管动脉压波动较大，但仍可提供充足的营养性血流。鉴于氧化代谢在大脑中的重要性，神经元活动的支持是通过向活性神经元提供足够的氧化底物的功能性充血来介导的。我们提供的数据表明，大脑中的这种功能性充血是由星形胶质细胞调节的，星形胶质细胞感知神经活动并释放扩张代谢物，将血流分流到活跃的神经元。在这方面，星形胶质细胞释放的代谢物之一是由 P450 酶形成的花生四烯酸 (AA) 的环氧化产物。 P450 酶的这些 AA 代谢物是环氧二十碳三烯酸 (EET)。其中一种 P450 酶由星形胶质细胞中的 2C11 cDNA 编码。此外，星形胶质细胞能够诱导毛细血管生成，这似乎部分是由 P450 衍生的 EET 介导的。
This short review summarizes the potential role of cytochrome P450 (P450) in regulating blood flow in the brain tissue and in the skeletal muscle. We provide data showing that pressure-induced myogenic activity in the brain is largely responsible for autoregulation of CBF. This myogenic response to pressure is maintained, in part, by 20-HETE formation in arterial muscle cells through a P450 omega-hydroxylase coded for by a P450 4A cDNA. Autoregulation of CBF is a hallmark of the cerebral circulation and provides adequate nutritive blood flow despite large fluctuations in arterial pressure. Given the importance of oxidative metabolism in the brain, support of neuronal activity is mediated by functional hyperaemia to active neurones providing adequate delivery of oxidative substrate. We provide data demonstrating that this functional hyperaemia in the brain is regulated by astrocytes which sense neural activity and release dilator metabolites which shunt blood flow to active neurones. One of the metabolites released by astrocytes in this regard are epoxygenated products of arachidonic acid (AA) formed by P450 enzymes. These AA metabolites of P450 enzymes are epoxyeicosatrienoic acid (EETs). One of these P450 enzymes is coded by a 2C11 cDNA present in astrocytes. Furthermore, astrocytes are capable of inducing capillary angiogenesis which appears to be mediated, in part, by P450-derived EETs.