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新生兔肝脏中线粒体腺嘌呤核苷酸含量的调节

Regulation of mitochondrial adenine nucleotide content in newborn rabbit liver.

作者信息

Tullson P C, Aprille J R

机构信息

Department of Biology, Tufts University, Medford, Massachusetts 02155.

出版信息

Am J Physiol. 1987 Nov;253(5 Pt 1):E530-5. doi: 10.1152/ajpendo.1987.253.5.E530.

Abstract

This study examined the relationship between postnatal metabolic and hormonal changes and the accompanying rapid increase in mitochondrial adenine nucleotide content (ATP + ADP + AMP) in rabbit liver. The cytosolic NAD+/NADH concentration ratio, calculated from tissue pyruvate and lactate values, increased linearly 6.6-fold during the 1st postnatal h. The mitochondrial NAD+/NADH concentration ratio, calculated from tissue acetoacetate and beta-hydroxybutyrate values, increased 28-fold by 30 min postnatal. These changes in NAD+/NADH suggest that tissue oxygenation occurs rapidly and that oxygen supply rather than substrate supply is limiting for mitochondrial respiration in the immediate postnatal period. The normal increase in mitochondrial adenine nucleotide content that occurs within 2 h after birth was inhibited by hypoxia (5% O2). Glucagon stimulated the postnatal increase in mitochondrial adenine nucleotides but had no effect in combination with hypoxia. Both glucose and somatostatin injections inhibited the increase in mitochondrial adenine nucleotides and increased the insulin-to-glucagon ratio. Isoproterenol or dibutyryl cAMP stimulated, but propranolol did not inhibit, the normal increase in mitochondrial adenine nucleotide content. Phentolamine did not stimulate the postnatal accumulation of adenine nucleotides. In summary, the results show that the insulin-to-glucagon ratio is probably the most important hormone regulator of the rapid recompartmentation of adenine nucleotides into the mitochondrial matrix and that tissue oxygenation is strictly permissive for this hormone effect in the first 2 h after birth.

摘要

本研究检测了家兔肝脏产后代谢和激素变化与伴随的线粒体腺嘌呤核苷酸含量(ATP + ADP + AMP)快速增加之间的关系。根据组织丙酮酸和乳酸值计算得出的胞质NAD⁺/NADH浓度比在出生后第1小时内呈线性增加,增长了6.6倍。根据组织乙酰乙酸和β-羟基丁酸值计算得出的线粒体NAD⁺/NADH浓度比在出生后30分钟时增加了28倍。NAD⁺/NADH的这些变化表明组织氧合迅速发生,并且在出生后即刻,氧气供应而非底物供应限制了线粒体呼吸。出生后2小时内线粒体腺嘌呤核苷酸含量的正常增加受到低氧(5% O₂)的抑制。胰高血糖素刺激了线粒体腺嘌呤核苷酸的产后增加,但与低氧联合使用时没有效果。葡萄糖和生长抑素注射均抑制了线粒体腺嘌呤核苷酸的增加,并提高了胰岛素与胰高血糖素的比值。异丙肾上腺素或二丁酰环磷腺苷刺激了线粒体腺嘌呤核苷酸含量的正常增加,但普萘洛尔并未抑制。酚妥拉明未刺激腺嘌呤核苷酸的产后积累。总之,结果表明胰岛素与胰高血糖素的比值可能是腺嘌呤核苷酸快速重新分配到线粒体基质中最重要的激素调节因子,并且在出生后的前2小时内,组织氧合对于这种激素效应是严格允许的。

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