Regulation of CO production in cerebral microvessels of newborn pigs
Regulation of CO production in cerebral microvessels of newborn pigs
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DOI：
10.1152/ajpheart.01059.2002
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发表时间：
2003-07-01
影响因子：
4.8
通讯作者：
Parfenova, H
中科院分区：
文献类型：
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作者：
Leffler, CW;Balabanova, L;Parfenova, H
一氧化碳 (CO) 由脑血管中的血红素加氧酶 2 (HO-2) 产生。使用气相色谱-质谱分析法对仔猪脑微血管进行分析，以验证 CO 产生受血红素输送和 HO-2 催化活性调节的假设。 CO 的产生似乎受到底物的限制，因为血红素及其前体氨基乙酰丙酸盐会增加 CO 的产生。离子霉素还可以增加二氧化碳的产生。然而，在富含钙的培养基、含有离子霉素的不含钙的培养基和含有离子霉素的富含钙的培养基中，外源血红素产生的CO是相同的。佛波醇肉豆蔻酸酯乙酸酯可增加 CO 产量，但不会改变 HO-2 的催化活性。此外，蛋白激酶C抑制剂1-(5-异喹啉基磺酰基)-2-甲基哌嗪对HO-2催化活性没有影响。蛋白酪氨酸激酶抑制会降低 HO-2 催化活性。抑制蛋白酪氨酸磷酸酶可增加 HO-2 催化活性。因此，脑微血管对 CO 产生的调节可以包括改变血红素可用性和 HO-2 催化活性。 HO-2 催化活性受到酪氨酸磷酸化的刺激。
Carbon monoxide (CO) is produced from heme by heme oxygenase-2 (HO-2) in cerebral blood vessels. Gas chromatography-mass spectrometry was used on piglet cerebral microvessels to address the hypothesis that CO production is regulated by heme delivery and HO-2 catalytic activity. CO production appears to be substrate limited because heme and its precursor aminolevulinate increase CO production. Ionomycin also increases CO production. However, CO production from exogenous heme was the same in Ca-replete medium, Ca-free medium with ionomycin, and Ca-replete medium with ionomycin. Phorbol myristate acetate increases CO production but does not change the catalytic activity of HO-2. Also, the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine has no effect on the HO-2 catalytic activity. Protein tyrosine kinase inhibition reduces HO-2 catalytic activity. Inhibition of protein tyrosine phosphatases increased HO-2 catalytic activity. Therefore, regulation of CO production by cerebral microvessels can include changing heme availability and HO-2 catalytic activity. HO-2 catalytic activity is stimulated by tyrosine phosphorylation.