Ogawa H, Ansai Y
Department of Biochemistry, Toyama Medical and Pharmaceutical University Faculty of Medicine, Japan.
Arch Biochem Biophys. 1995 Aug 1;321(1):115-22. doi: 10.1006/abbi.1995.1375.
It is generally accepted that a clock generating biological rhythms exists in the suprachiasmatic nuclei (SCN) of the hypothalamus in rodents. We have examined if diurnal variations of rat liver serine dehydratase (SDH), D-site binding protein (DBP), and 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGR) mRNA levels, each of which exhibits low values during the daytime (06:00-18:00) and high values during the dark period, are controlled by the SCN. The SCN were destructed electrolytically, and, 2 weeks later, rats were sacrificed at 06:00, 12:00, 18:00, and 24:00. Completeness of SCN lesions was assessed by the alteration of spontaneous locomotor activity and histological examination of the brains. The SDH and DBP mRNA levels in SCN-lesioned rats were very low at 06:00 and almost eliminated at 18:00, whereas the HMGR mRNA level at 06:00 was low at 06:00 and slightly increased at 18:00 compared to the control values. When determined at 12:00 and 24:00, the SDH, DBP, and HMGR mRNA levels in sham-operated rats were higher at 24:00 than at 12:00, whereas those in SCN-lesioned rats were higher at 12:00 than at 24:00. The hepatic beta-actin and glycine N-methyltransferase mRNA levels showed no significant diurnal variation and were not affected by SCN lesions. These results indicate that the SCN also play a pivotal role in determining rhythmic gene expression in liver.
一般认为,啮齿动物下丘脑的视交叉上核(SCN)中存在产生生物节律的时钟。我们研究了大鼠肝脏丝氨酸脱水酶(SDH)、D位点结合蛋白(DBP)和3-羟基-3-甲基戊二酰辅酶A还原酶(HMGR)mRNA水平的昼夜变化是否受SCN控制,这三种酶的mRNA水平在白天(06:00 - 18:00)均较低,而在黑暗期较高。用电解方法破坏SCN,2周后,在06:00、12:00、18:00和24:00处死大鼠。通过自发运动活动的改变和大脑组织学检查评估SCN损伤的完整性。SCN损伤大鼠的SDH和DBP mRNA水平在06:00时非常低,在18:00时几乎检测不到,而HMGR mRNA水平在06:00时较低,与对照值相比,在18:00时略有升高。在12:00和24:00测定时,假手术大鼠的SDH、DBP和HMGR mRNA水平在24:00时高于12:00,而SCN损伤大鼠的这些水平在12:00时高于24:00。肝脏β-肌动蛋白和甘氨酸N-甲基转移酶mRNA水平没有明显的昼夜变化,也不受SCN损伤的影响。这些结果表明,SCN在决定肝脏中节律性基因表达方面也起着关键作用。