Dale W E, Dang Y, Brown O R
Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO 65211, USA.
Free Radic Biol Med. 2000 Jul 15;29(2):191-8. doi: 10.1016/s0891-5849(00)00341-5.
We hypothesized that hyperbaric oxygen (HBO) enhances tryptophan (TRP) flux through the kynurenine (KYN) pathway because oxygen is a substrate for four pathway enzymes. Our objective was to compare the biosynthesis of KYN pathway intermediates by rat brain and liver slices with air or HBO as the gas phase. One-millimeter thick liver and brain slices were obtained from male Sprague-Dawley rats and incubated individually in chambers containing Hanks'-HEPES- buffer with (3)H-TRP (30 Ci/mmol) for 2 h (37 degrees C) in either room air or oxygen (1.2 or 5.2 atmospheres absolute [ATA] oxygen). After incubation, tissue was snap-frozen and analyzed for protein content while medium was extracted for high-performance liquid chromatography analysis. Radiolabeled nicotinamide adenine dinucleotide (NAD) was produced by brain and liver; liver (with air as the gas phase) also produced quinolinic acid (QA). HBO at 1.2 and 5.2 ATA caused increased QA and NAD from liver slices. HBO did not affect KYN metabolism in brain slices, although there was decreased production of NAD during high oxygen. We conclude that rat brain and liver contain the complete KYN pathway and that HBO enhances KYN flux in liver tissue.
我们推测，高压氧（HBO）可增强色氨酸（TRP）通过犬尿氨酸（KYN）途径的通量，因为氧气是该途径中四种酶的底物。我们的目的是比较以空气或HBO作为气相时，大鼠脑片和肝片对KYN途径中间产物的生物合成情况。从雄性Sprague-Dawley大鼠获取1毫米厚的肝片和脑片，分别置于含有Hanks'-HEPES缓冲液及（3）H-TRP（30 Ci/mmol）的培养箱中，在室温空气或氧气（1.2或5.2个绝对大气压[ATA]氧气）条件下于37℃孵育2小时。孵育后，将组织速冻并分析蛋白质含量，同时提取培养基用于高效液相色谱分析。脑和肝可产生放射性标记的烟酰胺腺嘌呤二核苷酸（NAD）；肝（以空气作为气相）还可产生喹啉酸（QA）。1.2和5.2 ATA的HBO可使肝片中的QA和NAD增加。HBO对脑片中的KYN代谢无影响，尽管在高氧条件下NAD的生成减少。我们得出结论，大鼠脑和肝含有完整的KYN途径，且HBO可增强肝组织中的KYN通量。
