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Localization and Age-Related Changes in Cytochrome P450 Expression in APA Hamster Livers

机译:在APA仓鼠肝脏中细胞色素P450表达的定位和与年龄相关的变化

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To establish the baseline data, age-related changes and the regional expression of the hepatic P450 isozymes in Syrian hamsters of the APA strain at 3, 6, 12, 18 months old were examined by immunological techniques. Immunohistochemical analysis of liver serial sections revealed that the midzonal and perivenous regions (zones 2 and 3, respectively) were stained with the anti-rat CYP1A1/2, 2B1/2 and 2E1 antibodies. These three antibodies most intensely stained the hepatocytes around the central vein. An anti-rat CYP3A2 staining section had a staining pattern with equally intense reactions in zones 2 and 3. On the other hand, CYP2C6, 2C11 and 4A1 were distributed diffusely throughout the hepatic acinus. There was no age-related difference in the expression pattern of any of the P450 isozymes examined. Total P450 content had a peak at 6 months of age and decreased to 60% of that level thereafter. Western-blot analysis revealed that the peak expressions of the isozymes detected with anti-rat CYP1A1/2, 2C6, 2E1 and 3A2 antibodies were observed in 6-month-old hamsters and declined in older ones. The CYP2B and 2C11 content reached the maximum at the age of 6 months and maintained almost the same level thereafter. The CYP4A level did not change from 3 to 6 months, and then declined to about 40% of the younger level at 12 and 18 months of age. These results suggest that the hepatic P450 isozymes of APA hamsters have region-specific expressions and most isozymes have their peaks of expression at 6 months of age, which differs from the patterns for rat P450.
机译:为了建立基线数据,通过免疫技术检查了3、6、12、18个月大时APA菌株叙利亚仓鼠中与年龄相关的变化和肝脏P450同工酶的区域表达。肝连续切片的免疫组织化学分析显示,中区和静脉区(分别为2区和3区)被抗大鼠CYP1A1 / 2、2B1 / 2和2E1抗体染色。这三种抗体对中心静脉周围的肝细胞染色最深。抗大鼠CYP3A2染色部分在2区和3区具有同样强烈反应的染色模式。另一方面,CYP2C6、2C11和4A1散布在整个肝腺泡中。在所检查的任何P450同工酶的表达模式中都没有年龄相关的差异。总P450含量在6个月大时达到峰值,此后降至该水平的60%。 Western-blot分析显示,在6个月大的仓鼠中观察到用抗大鼠CYP1A1 / 2、2C6、2E1和3A2抗体检测到的同工酶的峰值表达,而在较早的仓鼠中下降。 CYP2B和2C11的含量在6个月时达到最大值,此后保持几乎相同的水平。 CYP4A水平从3个月到6个月没有变化,然后下降到12和18个月大时年轻水平的40%。这些结果表明,APA仓鼠的肝P450同工酶具有区域特异性表达,大多数同工酶在6个月大时具有其表达高峰,这与大鼠P450的模式不同。

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