Kim H S, Jung Y Y, Do S I
Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Braz J Med Biol Res. 2014 Nov;47(11):940-6. doi: 10.1590/1414-431X20143834. Epub 2014 Aug 29.
Stimulation by a number of conditions, including infection, cytokines, mechanical injury, and hypoxia, can upregulate inducible nitric oxide synthase (iNOS) in hepatocytes. We observed that exposure to hypergravity significantly upregulated the transcription of the hepatic iNOS gene. The aim of this study was to confirm our preliminary data, and to further investigate the distribution of the iNOS protein in the livers of mice exposed to hypergravity. ICR mice were exposed to +3 Gz for 1 h. We investigated the time course of change in the iNOS expression. Hepatic iNOS mRNA expression progressively increased in centrifuged mice from 0 to 12 h, and then decreased rapidly by 18 h. iNOS mRNA levels in the livers of centrifuged mice was significantly higher at 3, 6, and 12 h than in uncentrifuged control mice. The pattern of iNOS protein expression paralleled that of the mRNA expression. At 0 and 1 h, weak cytoplasmic iNOS immunoreactivity was found in some hepatocytes surrounding terminal hepatic venules. It was noted that at 6 h there was an increase in the number of perivenular hepatocytes with moderate to strong cytoplasmic immunoreactivity. The number of iNOS-positive hepatocytes was maximally increased at 12 h. The majority of positively stained cells showed a strong intensity of iNOS expression. The expression levels of iNOS mRNA and protein were significantly increased in the livers of mice exposed to hypergravity. These results suggest that exposure to hypergravity significantly upregulates iNOS at both transcriptional and translational levels.
包括感染、细胞因子、机械损伤和缺氧在内的多种条件刺激可上调肝细胞中的诱导型一氧化氮合酶（iNOS）。我们观察到暴露于超重环境会显著上调肝脏iNOS基因的转录。本研究的目的是证实我们的初步数据，并进一步研究超重环境下小鼠肝脏中iNOS蛋白的分布情况。将ICR小鼠暴露于+3 Gz环境1小时。我们研究了iNOS表达的时间变化过程。离心处理的小鼠肝脏中iNOS mRNA表达在0至12小时逐渐增加，然后在18小时迅速下降。离心处理小鼠肝脏中iNOS mRNA水平在3、6和12小时显著高于未离心的对照小鼠。iNOS蛋白表达模式与mRNA表达模式相似。在0和1小时，在终末肝静脉周围的一些肝细胞中发现微弱的细胞质iNOS免疫反应性。值得注意的是，在6小时，静脉周围具有中度至强细胞质免疫反应性的肝细胞数量增加。iNOS阳性肝细胞数量在12小时达到最大增加。大多数阳性染色细胞显示iNOS表达强度较强。暴露于超重环境的小鼠肝脏中iNOS mRNA和蛋白的表达水平显著增加。这些结果表明，暴露于超重环境会在转录和翻译水平上显著上调iNOS。
