Altered expression and function of mitochondrial β-oxidation enzymes in juvenile intrauterine-growth-retarded rat skeletal muscle
Altered expression and function of mitochondrial β-oxidation enzymes in juvenile intrauterine-growth-retarded rat skeletal muscle
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DOI：
10.1203/00006450-200107000-00016
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发表时间：
2001-07-01
影响因子：
3.6
通讯作者：
Gruetzmacher, EM
中科院分区：
文献类型：
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作者：
Lane, RH;Kelley, DE;Gruetzmacher, EM
子宫胎盘功能不全和随后的宫内生长迟缓(IUGR)会影响出生后的代谢。在幼年大鼠中，IUGR改变了骨骼肌线粒体基因的表达，降低了线粒体NAD+/NADH比率，这两者都影响β-氧化通量。因此，我们假设在幼年IUGR骨骼肌中线粒体β-氧化酶的基因表达和功能将发生改变。为了验证这一假说，我们对21日龄(断奶前)IUGR和对照组大鼠骨骼肌中5种关键的线粒体酶(肉碱棕榈酰转移酶I、三功能蛋白β氧化、解偶联蛋白3、异柠檬酸脱氢酶和线粒体苹果酸脱氢酶)和肌内甘油三酯的mRNA水平进行了定量研究。在分离的骨骼肌线粒体中，由于β-氧化和异柠檬酸脱氢酶这两种酶竞争线粒体，所以对这两种酶的酶功能进行了测定。NAD(+)。IUGR骨骼肌肉碱棕榈酰基转移酶I、β氧化三功能蛋白和解偶联蛋白3mRNA水平显著升高，而异柠檬酸脱氢酶和线粒体苹果酸脱氢酶的mRNA水平无明显变化。同样，IUGR骨骼肌线粒体中三功能蛋白的β-氧化活性增加，异柠檬酸脱氢酶活性不变。有趣的是，在IUGR骨骼肌中，骨骼肌甘油三酯显著增加。我们得出结论，子宫胎盘功能不全改变了IUGR骨骼肌线粒体脂质代谢，我们推测本研究中观察到的变化在IUGR相关的长期发病率中发挥了作用。
Uteroplacental insufficiency and subsequent intrauterine growth retardation (IUGR) affects postnatal metabolism. In juvenile rats, IUGR alters skeletal muscle mitochondrial gene expression and reduces mitochondrial NAD+/NADH ratios, both of which affect beta -oxidation flux. We therefore hypothesized that gene expression and function of mitochondrial beta -oxidation enzymes would be altered in juvenile IUGR skeletal muscle. To test this hypothesis, mRNA levels of five key mitochondrial enzymes (carnitine palmitoyltransferase I, trifunctional protein of beta -oxidation, uncoupling protein-3, isocitrate dehydrogenase, and mitochondrial malate dehydrogenase) and intramuscular triglycerides were quantified in 21-d-old (preweaning) IUGR and control rat skeletal muscle. In isolated skeletal muscle mitochondria, enzyme function of the trifunctional protein of beta -oxidation and isocitrate dehydrogenase were measured because both enzymes compete for mitochondrial. NAD(+). Carnitine palmitoyltransferase I, the trifunctional protein of beta -oxidation and uncoupling protein 3 mRNA levels were significantly increased in IUGR skeletal muscle, whereas mRNA levels of isocitrate dehydrogenase and mitochondrial malate dehydrogenase were unchanged. Similarly, trifunctional protein of beta -oxidation activity was increased in IUGR skeletal muscle mitochondria, and isocitrate dehydrogenase activity was unchanged. Interestingly, skeletal muscle triglycerides were significantly increased in IUGR skeletal muscle. We conclude that uteroplacental insufficiency alters IUGR skeletal muscle mitochondrial lipid metabolism, and we speculate that the changes observed in this study play a role in the long-term morbidity associated with IUGR.