Kelly D P, Gordon J I, Alpers R, Strauss A W
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110.
J Biol Chem. 1989 Nov 15;264(32):18921-5.
To study the regulation of nuclear genes which encode mitochondrial enzymes involved in oxidative metabolism, absolute levels of mRNA encoding rat medium chain acyl-CoA dehydrogenase (MCAD) and rat mitochondrial malate dehydrogenase (mMDH) were determined in developing and adult male rat tissues. MCAD mRNA is expressed in a variety of adult male tissues with highest steady state levels in heart, adrenal, and skeletal muscle and lowest levels in brain, lung, and testes. In comparison, steady state levels of mMDH mRNA in adult male rat tissues were similar to those of MCAD mRNA in heart, small intestine, adrenal, and skeletal muscle but markedly different in brain, stomach, and testes. Thus, the steady-state levels of MCAD and mMDH mRNA are highest in adult tissues with high energy requirements. Dot blot analysis of RNA prepared from late fetal, suckling, and weaning rat heart, liver, and brain demonstrated the presence of MCAD and mMDH mRNA during the fetal period in all three tissues. Both MCAD and mMDH mRNA levels increased 2-2.5-fold at birth followed by a decline during the first postnatal week in heart and liver. The patterns of accumulation of these mRNAs in heart and liver during the weaning and early adult periods were also similar, although the absolute levels were significantly different. Brain MCAD mRNA levels were consistently low (less than 0.1 pg/micrograms total cellular RNA) throughout the developmental stages. However, brain mMDH mRNA levels exhibited a marked increase during the weaning period, reaching a peak concentration which is higher than the level of mMDH mRNA in heart and liver at any point during development. These results indicate that the level of expression of the nuclear genes encoding MCAD and mMDH is tissue-specific and developmentally regulated. The patterns of MCAD and mMDH mRNA accumulation parallel the changes in energy metabolism which occur during development and among adult tissues.
为研究编码参与氧化代谢的线粒体酶的核基因调控，测定了发育中和成年雄性大鼠组织中编码大鼠中链酰基辅酶A脱氢酶（MCAD）和大鼠线粒体苹果酸脱氢酶（mMDH）的mRNA的绝对水平。MCAD mRNA在成年雄性大鼠的多种组织中表达，在心脏、肾上腺和骨骼肌中的稳态水平最高，在脑、肺和睾丸中的水平最低。相比之下，成年雄性大鼠组织中mMDH mRNA的稳态水平在心脏、小肠、肾上腺和骨骼肌中与MCAD mRNA相似，但在脑、胃和睾丸中明显不同。因此，MCAD和mMDH mRNA的稳态水平在能量需求高的成年组织中最高。对来自晚期胎儿、哺乳期和断奶期大鼠心脏、肝脏和脑的RNA进行斑点印迹分析表明，在胎儿期所有这三种组织中均存在MCAD和mMDH mRNA。出生时MCAD和mMDH mRNA水平均增加2 - 2.5倍，随后在出生后的第一周心脏和肝脏中下降。在断奶期和成年早期，心脏和肝脏中这些mRNA的积累模式也相似，尽管绝对水平有显著差异。在整个发育阶段，脑MCAD mRNA水平一直很低（低于0.1 pg/微克总细胞RNA）。然而，脑mMDH mRNA水平在断奶期显著增加，达到的峰值浓度高于发育过程中任何时候心脏和肝脏中mMDH mRNA的水平。这些结果表明，编码MCAD和mMDH的核基因的表达水平具有组织特异性且受发育调控。MCAD和mMDH mRNA积累模式与发育过程中和成年组织间能量代谢的变化平行。
