Kynurenine Pathway Enzymes in Brain: Responses to Ischemic Brain Injury Versus Systemic Immune Activation
Kynurenine Pathway Enzymes in Brain: Responses to Ischemic Brain Injury Versus Systemic Immune Activation
复制标题
大脑中的犬尿氨酸途径酶：对缺血性脑损伤的反应与全身免疫激活
作者：
K. Saito;T. Nowak;K. Suyama;B. Quearry;M. Saito;J. Crowley;S. Markey;M. Heyes
脑内L-犬尿氨酸和喹啉酸(Quin)的蓄积发生在缺血性脑损伤或全身给予商陆有丝分裂原后。虽然在正常沙土鼠和给予商陆丝裂原的沙土鼠脑中都没有发现L-[13C6]色氨酸向[13C6]-Quin的转化，但在短暂性脑缺血4天后，脑组织中确实发生了直接转化。吲哚-2，3-双加氧酶远端的酶活性增加可能决定L-犬尿氨酸是否转化为奎宁。脑缺血10min后1d，海马区犬尿氨酸酶和3-羟基-3，4-双加氧酶活性升高，而局部奎宁水平和吲哚-2，3-双加氧酶和犬尿氨酸-3-羟基酶活性无明显变化。然而，在缺血后第2天和第4天，所有这些酶在海马区的活性以及奎宁水平都显著增加。海马区犬尿氨酸转氨酶活性在缺血后第1天和第2天没有变化，但在第4天有所下降，此时局部犬尿酸水平没有变化。在正常或缺血4天的沙土鼠的海马体中，Quin的假定前体[13C6]邻氨基苯甲酸不能转化为[13C6]-Quin。沙土鼠巨噬细胞在体外受内毒素刺激后，将L-[13C6]色氨酸转化为[13Ce]Quin。对沙土鼠大脑皮质犬尿氨酸-3-羟基酶活性的动态分析表明，缺血后脑组织Vmax增加，Km无变化。系统给予商陆丝裂原可增加脑组织中吲哚-2，3-双加氧酶和犬尿氨酸酶的活性，但对犬尿氨酸-3-羟基酶或3-羟基邻氨基苯甲酸酯-3，4-双加氧酶的活性无明显影响。犬尿氨酸-3-羟基酶活性的升高，以及脑损伤部位巨噬细胞中吲哚-2，3-双加氧酶、犬尿氨酸酶和3-羟基邻氨基苯甲酸-3，4-双加氧酶的诱导，可能解释了脑缺血后海马将L-[13C6]色氨酸转化为[13C6]Quin的能力。
Accumulation of l‐kynurenine and quinolinic acid (QUIN) in the brain occurs after either ischemic brain injury or after systemic administration of pokeweed mitogen. Although conversion of l‐[13C6]tryptophan to [13C6]‐QUIN has not been demonstrated in brain either from normal gerbils or from gerbils given pokeweed mitogen, direct conversion in brain tissue does occur 4 days after transient cerebral ischemia. Increased activities of enzymes distal to indoleamine‐2,3‐dioxygenase may determine whether l‐kynurenine is converted to QUIN. One day after 10 min of cerebral ischemia, the activities of kynureninase and 3‐hydroxy‐3,4‐dioxygenase were increased in the hippocampus, but local QUIN levels and the activities of the indoleamine‐2,3‐dioxygenase and kynurenine‐3‐hydroxylase were unchanged. By days 2 and 4 after ischemia, however, the activities of all of these enzymes in the hippocampus as well as QUIN levels were significantly increased. Kynurenine aminotransferase activity in the hippocampus was unchanged on days 1 and 2 after ischemia but was decreased on day 4, at a time when local kynurenic acid levels were unchanged. A putative precursor of QUIN, [13C6]anthranilic acid, was not converted to [13C6]‐QUIN in the hippocampus of either normal or 4‐day postischemic gerbils. Gerbil macrophages stimulated by endo‐toxin in vitro converted l‐[13C6]tryptophan to [13Ce]QUIN. Kinetic analysis of kynurenine‐3‐hydroxylase activity in the cerebral cortex of postischemic gerbils showed that Vmax increased, without changes in Km. Systemic administration of pokeweed mitogen increased indoleamine‐2,3‐dioxygenase and kynureninase activities in the brain without significant changes in kynurenine‐3‐hydroxylase or 3‐hydroxyanthranilate‐3,4‐dioxygenase activities. Increases in kynurenine‐3‐hydroxylase activity, in conjunction with induction of indoleamine‐2,3‐dioxygenase, kynureninase, and 3‐hydroxyanthranilate‐3,4‐dioxygenase in macro‐phage infiltrates at the site of brain injury, may explain the ability of postischemic hippocampus to convert l‐[13C6]tryptophan to [13C6]QUIN.
影响因子：
15.9
作者：
ACHIM, CL;HEYES, MP;WILEY, CA
通讯作者：
WILEY, CA
毒油综合征和嗜酸性粒细胞增多肌痛综合征中色氨酸代谢的改变。
DOI：
--
发表时间：
1992
期刊：
The Journal of rheumatology
影响因子：
--
作者：
Silver,RM;Sutherland,SE;Carreira,P;Heyes,MP
通讯作者：
Heyes,MP
DOI：
10.1073/pnas.85.11.4079
发表时间：
1988-06-01
影响因子：
11.1
作者：
SCHWARCZ, R;OKUNO, E;WHETSELL, WO
通讯作者：
WHETSELL, WO