Rossignol Fabrice, Solares Magali, Balanza Elfride, Coudert Jean, Clottes Eric
Laboratoire Inter-Universitaire des Activités Physiques et Sportives, Faculté de Médecine, 28 Place Henri Dunant, 63001 Clermont-Ferrand Cedex, France.
J Cell Biochem. 2003 May 1;89(1):67-79. doi: 10.1002/jcb.10484.
Lactate dehydrogenase (LDH) is a tetramer made up of two different subunits A and B. In cellular models, severe hypoxia increases LDH A gene expression whereas LDH B gene does not exhibit any regulation. The aim of our work was to characterise LDH expression in different tissues of rats bred at high altitude. For this purpose, we chose a Sprague-Dawley rat strain adapted to chronic hypoxia in La Paz (3700 m), Bolivia. Two normoxic control groups were bred at low altitude in Clermont-Ferrand (350 m), France, one group was ad libitum with free access to food and water as was the hypoxic one, and the second normoxic group was nourished with the food intakes measured for the animals from La Paz. We measured total LDH specific activity, isoform distribution and LDH A and B mRNA amounts in three skeletal muscles (soleus, extensor digitorum longus (EDL), plantaris), heart and brain. Our study demonstrates that, unlike what has been shown in cellular models under severe hypoxia, LDH A gene is not systematically up-regulated in tissues of rats living at high altitude. Furthermore, chronic hypoxia limits LDH B gene transcription or its mRNA stability in both soleus and EDL. These regulations occur at various molecular levels like gene transcription, mRNA stabilisation or translation and protein stability, depending on the tissue studied, and are partly attributed to caloric restriction provoked by high altitude. These data provide insight into LDH gene expression underlying the diverse and complex tissue-specific response to chronic hypoxia.
乳酸脱氢酶（LDH）是一种由两种不同亚基A和B组成的四聚体。在细胞模型中，严重缺氧会增加LDH A基因的表达，而LDH B基因则未表现出任何调控。我们研究的目的是表征在高海拔地区饲养的大鼠不同组织中LDH的表达。为此，我们选择了一种适应玻利维亚拉巴斯（3700米）慢性缺氧的斯普拉格-道利大鼠品系。两个常氧对照组在法国克莱蒙费朗（350米）的低海拔地区饲养，一组与缺氧组一样可自由获取食物和水，另一常氧组则按照为拉巴斯的动物测量的食物摄入量进行喂养。我们测量了三种骨骼肌（比目鱼肌、趾长伸肌（EDL）、跖肌）、心脏和大脑中的总LDH比活性、同工型分布以及LDH A和B mRNA的量。我们的研究表明，与在严重缺氧的细胞模型中所显示的情况不同，生活在高海拔地区的大鼠组织中LDH A基因并非系统性地上调。此外，慢性缺氧会限制比目鱼肌和EDL中LDH B基因的转录或其mRNA的稳定性。这些调控发生在基因转录、mRNA稳定化或翻译以及蛋白质稳定性等不同分子水平，具体取决于所研究的组织，并且部分归因于高海拔引起的热量限制。这些数据为深入了解慢性缺氧的多样且复杂的组织特异性反应背后的LDH基因表达提供了线索。
