Mitochondrial content and distribution changes specific to mouse diaphragm after chronic normobaric hypoxia
Mitochondrial content and distribution changes specific to mouse diaphragm after chronic normobaric hypoxia
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DOI：
10.1152/ajpregu.00320.2009
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发表时间：
2010-03-01
影响因子：
2.8
通讯作者：
Andrade, Francisco H.
中科院分区：
文献类型：
--
作者：
Gamboa, Jorge L.;Andrade, Francisco H.
Gbo a JL、Andrade FH.慢性常压低氧后小鼠膈肌线粒体含量和分布的变化。Am J Physiol Regul Integr Comp Physiol 298：R575-R583,2010.首次发表于2009年12月9日；doi：10.1152/ajpregu.00320.2009。-慢性低氧降低肢体骨骼肌的有氧能力(线粒体含量)，其中一个原因似乎是体力活动减少。然而，当低氧增加呼吸功时，横隔肌和其他呼吸肌可能会有不同的适应模式。因此，我们假设慢性缺氧不会减少小鼠横隔膜中线粒体的含量。成年雄性C57BL/6J小鼠分别在常氧(FiO2=21%，对照组)和常压低氧(FiO2=10%，低氧)中饲养1、2、4wk。然后处死小鼠，收集横隔肌和腓肠肌进行分析。在隔膜，细胞色素c氧化酶组织化学染色显示缺氧组染色较弱。用Western印迹法检测电子传递链、丙酮酸脱氢酶激酶1(PDK1)和电压依赖性阴离子通道1(VDAC1)亚基的总含量。在低氧4周后，这些蛋白质减少了25-30%(P<；0.05与对照组相比)，与隔膜线粒体体密度的下降一致(对照组为33.6+/-5.5%，低氧为26.8+/-6.7%，P=0.013)。缺氧后腓肠肌线粒体体密度和蛋白质含量无明显变化。低氧可降低膜组织中PPARγ和PPARγ辅因子1α(PGC 1α)的含量，但对腓肠肌无明显影响。低氧组大鼠膈肌组织中PGC-1α基因表达水平也明显降低。BCL2/腺病毒E1B相互作用蛋白3(BNIP-3)在缺氧1wk和2wk分别在隔肌和腓肠肌中表达上调，BNIP-3蛋白含量仅在缺氧4wk时才在隔膜增加。与我们的假设相反，这些结果表明，尽管工作负荷增加，但慢性低氧减少了小鼠横隔膜中线粒体的含量。线粒体生物发生减少和线粒体吞噬增加的共同作用似乎是低氧后小鼠膈肌线粒体含量减少的原因。
Gamboa JL, Andrade FH. Mitochondrial content and distribution changes specific to mouse diaphragm after chronic normobaric hypoxia. Am J Physiol Regul Integr Comp Physiol 298: R575-R583, 2010. First published December 9, 2009; doi:10.1152/ajpregu.00320.2009.-Chronic hypoxia reduces aerobic capacity (mitochondrial content) in limb skeletal muscles, and one of the causes seems to be decreased physical activity. Diaphragm and other respiratory muscles, however, may have a different pattern of adaptation as hypoxia increases the work of breathing. Thus, we hypothesized that chronic hypoxia would not reduce mitochondrial content in mouse diaphragm. Adult male C57BL/6J mice were kept in normoxia (FIO2 = 21%, control) or normobaric hypoxia (FIO2 = 10%, hypoxia) for 1, 2, and 4 wk. Mice were then killed, and the diaphragm and gastrocnemius muscles collected for analysis. In the diaphragm, cytochrome c oxidase histochemistry showed less intense staining in the hypoxia group. The total content of subunits from the electron transport chain, pyruvate dehydrogenase kinase 1 (PDK1), and voltage-dependent anion channel 1 (VDAC1) was evaluated by Western blot. These proteins decreased by 25-30% after 4 wk of hypoxia (P < 0.05 vs. control for all comparisons), matching a comparable decrease in diaphragmatic mitochondrial volume density (control 33.6 +/- 5.5% vs. hypoxia 26.8 +/- 6.7%, P = 0.013). Mitochondrial volume density or protein content did not change in gastrocnemius after hypoxia. Hypoxia decreased the content of peroxisome proliferator-activated receptor gamma (PPAR gamma) and PPAR gamma cofactor 1-alpha (PGC-1 alpha) in diaphragm but not in gastrocnemius. PGC-1 alpha mRNA levels in diaphragm were also reduced with hypoxia. BCL2/adenovirus E1B interacting protein 3 (BNIP-3) mRNA levels were upregulated after 1 and 2 wk of hypoxia in diaphragm and gastrocnemius, respectively; BNIP-3 protein content increased only in the diaphragm after 4 wk of hypoxia. Contrary to our hypothesis, these results show that chronic hypoxia decreases mitochondrial content in mouse diaphragm, despite the increase in workload. A combination of reduced mitochondrial biogenesis and increased mitophagy seems to be responsible for the decrease in mitochondrial content in the mouse diaphragm after hypoxia.