Analysis of gene and protein expression of cytochrome P450 and stress-associated molecules in rat liver after spaceflight
Analysis of gene and protein expression of cytochrome P450 and stress-associated molecules in rat liver after spaceflight
复制标题
DOI：
10.1111/j.1440-1827.2008.02275.x
复制
发表时间：
2008-09-01
影响因子：
2.2
通讯作者：
Fukumoto, Manabu
中科院分区：
文献类型：
--
作者：
Baba, Taisuke;Nishimura, Masuhiro;Fukumoto, Manabu
随着空间飞行次数的增加和飞行时间的延长，对机组人员使用药剂的需要可能会增加。最终目标是预测药物的治疗或毒性作用，特别是那些治疗指数低的药物。肝脏是全身代谢的中心，因此，各种药物依赖于细胞色素P450（CYP）的肝脏代谢。由于受不同的调节机制和底物特异性的影响，因此单个β-内酰胺酶的功能是多种多样的。由于航天飞行可能是一种应激源，并单独影响每一个β-淀粉样蛋白的表达，本研究的目的是测量11个β-淀粉样蛋白基因的表达和蛋白质分布在航天飞行后的大鼠肝脏，分别使用实时聚合酶链反应和免疫组化。此外，还测定了冷诱导RNA结合蛋白（Cirp）、热休克蛋白70（HSP70）、HSP90和p53肿瘤抑制基因等应激相关蛋白的基因和蛋白表达。与地面对照组相比，飞行组CYP4A1和Cirp基因表达显著升高，而HSP 90和p53基因表达显著降低。结合组织学分析，认为航天对肝脏的影响可能类似于轻度冷应激或禁食。
As the incidence and length of spaceflight increases, the need to administer pharmacological agents to crew members may become greater. The final goal is to predict the therapeutic or toxic effects of drugs, especially those with a low therapeutic index, during spaceflight. The liver is central to systemic metabolism, therefore, various drugs rely on hepatic metabolism by cytochrome P450 (CYP). The function of individual CYP enzymes is diverse because they are subject to different regulatory mechanisms and substrate specificity. Because spaceflight may be a stressor and influence each CYP expression individually, the purpose of the present study was to measure the expression of 11 CYP genes and protein distribution in the liver of rats after spaceflight, using real-time polymerase chain reaction and immunohistochemistry, respectively. The gene and protein expression of stress-related proteins such as cold-inducible RNA binding protein (Cirp), heat shock protein 70 (HSP70), HSP90 and the p53 tumor suppressor gene, were also determined. CYP4A1and Cirp gene expression was significantly increased whereas HSP90 and p53 gene expression was significantly decreased in the flight group than in the ground control. Combined with histology, it is concluded that the effects of spaceflight on the liver may be similar to mild cold stress or fasting.