Homeostatic imbalance of purine catabolism in first-episode neuroleptic-naïve patients with schizophrenia.
Homeostatic imbalance of purine catabolism in first-episode neuroleptic-naïve patients with schizophrenia.
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DOI：
10.1371/journal.pone.0009508
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发表时间：
2010-03-03
期刊：
影响因子：
3.7
通讯作者：
Kaddurah-Daouk R
中科院分区：
文献类型：
--
作者：
Yao JK;Dougherty GG Jr;Reddy RD;Keshavan MS;Montrose DM;Matson WR;McEvoy J;Kaddurah-Daouk R
嘌呤分解代谢可能是线粒体对氧化应激稳态反应的一个未被认识的重要组成部分。越来越多的证据表明氧化应激在精神分裂症病理中起着关键作用。使用高压液相色谱联用库仑多电极阵列系统，我们比较了首发neuroleptic-naïve精神分裂症患者（FENNS, n = 25）和健康对照（HC, n = 30）以及FENNS在基线（BL）和抗精神病药物治疗后4周（4w）血浆中的6种嘌呤代谢物。与HC患者相比，两组患者的黄嘌呤（Xant）水平均显著升高，鸟嘌呤(G)水平显著降低。G/鸟苷（Gr）、尿酸(UA)/Gr和UA/Xant比值显著低于HC，而Xant/G比值显著高于HC。这些变化在FENNS-4w中仍然存在，只是UA/Gr的比值归一化了。3组血清G与UA、Xan与次黄嘌呤（Hx）均呈显著相关。相比之下，UA与Xan和Hx的相关性以及Xan与Gr的相关性在HC中都非常显著，而在FENNS中则不显著。最后，Gr与UA和G的相关性在HC和fnns - bl中均显著，而在fnns -4w中不显著。在嘌呤分解代谢过程中，Gr到G和Xant到Xan的转化都是可逆的。产物与前体的比例降低表明有利于Xant从Xan产生的转变，导致FENNS中的UA水平降低。具体而言，在抗精神病药物治疗4周后，降低的UA/Gr比率几乎正常化。此外，嘌呤通路中存在紧密相关的前体和产物关系；尽管其中一些相关性在疾病或药物状态中持续存在，但其他相关性似乎在fenn中消失了。综上所述，这些结果表明，嘌呤分解代谢稳定形成抗氧化UA的潜力在疾病早期就发生了改变。
Purine catabolism may be an unappreciated, but important component of the homeostatic response of mitochondria to oxidant stress. Accumulating evidence suggests a pivotal role of oxidative stress in schizophrenia pathology. Using high-pressure liquid chromatography coupled with a coulometric multi-electrode array system, we compared 6 purine metabolites simultaneously in plasma between first-episode neuroleptic-naïve patients with schizophrenia (FENNS, n = 25) and healthy controls (HC, n = 30), as well as between FENNS at baseline (BL) and 4 weeks (4w) after antipsychotic treatment. Significantly higher levels of xanthosine (Xant) and lower levels of guanine (G) were seen in both patient groups compared to HC subjects. Moreover, the ratios of G/guanosine (Gr), uric acid (UA)/Gr, and UA/Xant were significantly lower, whereas the ratio of Xant/G was significantly higher in FENNS-BL than in HC. Such changes remained in FENNS-4w with exception that the ratio of UA/Gr was normalized. All 3 groups had significant correlations between G and UA, and Xan and hypoxanthine (Hx). By contrast, correlations of UA with each of Xan and Hx, and the correlation of Xan with Gr were all quite significant for the HC but not for the FENNS. Finally, correlations of Gr with each of UA and G were significant for both HC and FENNS-BL but not for the FENNS-4w. During purine catabolism, both conversions of Gr to G and of Xant to Xan are reversible. Decreased ratios of product to precursor suggested a shift favorable to Xant production from Xan, resulting in decreased UA levels in the FENNS. Specifically, the reduced UA/Gr ratio was nearly normalized after 4 weeks of antipsychotic treatment. In addition, there are tightly correlated precursor and product relationships within purine pathways; although some of these correlations persist across disease or medication status, others appear to be lost among FENNS. Taken together, these results suggest that the potential for steady formation of antioxidant UA from purine catabolism is altered early in the course of illness.
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影响因子：
4.5
作者：
Hayden MR;Tyagi SC
通讯作者：
Tyagi SC
DOI：
10.1073/pnas.78.11.6858
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
AMES, BN;CATHCART, R;HOCHSTEIN, P
通讯作者：
HOCHSTEIN, P
影响因子：
8.3
作者：
Bos, Michiel J.;Koudstaal, Peter J.;Breteler, Monique M. B.
通讯作者：
Breteler, Monique M. B.
影响因子：
14.5
作者：
Bogdanov, Mikhail;Matson, Wayne R.;Beal, M. Flint
通讯作者：
Beal, M. Flint
影响因子：
3.8
作者：
Gysin, Rene;Riederer, Irene M.;Riederer, Beat M.
通讯作者：
Riederer, Beat M.