Age-dependent regulation of skeletal muscle mitochondria by the thrombospondin-1 receptor CD47.
Age-dependent regulation of skeletal muscle mitochondria by the thrombospondin-1 receptor CD47.
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DOI：
10.1016/j.matbio.2010.12.004
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发表时间：
2011-03
期刊：
影响因子：
6.9
通讯作者：
Frazier, William A.
中科院分区：
文献类型：
--
作者：
Frazier, Elfaridah P.;Isenberg, Jeff S.;Shiva, Sruti;Zhao, Lei;Schlesinger, Paul;Dimitry, Julie;Abu-Asab, Mones S.;Tsokos, Maria;Roberts, David D.;Frazier, William A.
关键词：
CD47是凝血酶敏感蛋白-1的受体，限制了两个重要的调节轴：一氧化氮-cGMP信号和cAMP信号，这两个信号都能促进线粒体的生物发生。电子显微镜显示CD47缺失和血栓反应蛋白-1缺失的小鼠骨骼肌中线粒体密度增加。我们进一步评估了CD47缺失的小鼠与WT小鼠的线粒体状态。从3月龄小鼠的组织中提取的RNA的定量RT-PCRNAs显示，编码线粒体蛋白的mRNAs和pGC-1mRNAs在CD47零基因缺失的小鼠的快、慢抽动骨骼肌中的表达显著增加，而在其他组织中几乎没有表达。线粒体蛋白的Western blotting证实了这些观察到的结果。CD47缺失细胞和WT细胞线粒体的电子传递酶相对含量和ATP/O2比值无明显差异。与WTS相比，CD47缺失的年轻小鼠表现出更高的跑步机耐力，CD47缺失的腓肠肌经历了肌红蛋白和肌球蛋白重链表达的缓慢抽动模式的纤维类型转换。12月龄小鼠骨骼肌线粒体体密度和耐力均下降至野生型水平。在腓肠肌中，肌球蛋白重链亚型和肌红蛋白的表达也恢复到快速抽动模式。CD47和TSP1缺失的小鼠都比WTS小鼠瘦，比WT小鼠消耗更少的氧气，产生的热量也更少。CD47缺失的细胞比WT细胞产生的活性氧要少得多。这些数据表明，TSP1-CD47系统信号的丢失促进了正常功能线粒体的组织特异性和年龄依赖性的积累，从而提高了体能，降低了活性氧的产生，并提高了代谢效率。
CD47, a receptor for thrombospondin-1, limits two important regulatory axes: nitric oxide-cGMP signaling and cAMP signaling, both of which can promote mitochondrial biogenesis. Electron microscopy revealed increased mitochondrial densities in skeletal muscle from both CD47 null and thrombospondin-1 null mice. We further assessed the mitochondria status of CD47-null vs WT mice. Quantitative RT-PCR of RNA extracted from tissues of 3 month-old mice revealed dramatically elevated expression of mRNAs encoding mitochondrial proteins and PGC-1α in both fast and slow twitch skeletal muscle from CD47-null mice, but modest to no elevation in other tissues. These observations were confirmed by Western blotting of mitochondrial proteins. Relative amounts of electron transport enzymes and ATP/O2 ratios of isolated mitochondria were not different between mitochondria from CD47-null and WT cells. Young CD47-null mice displayed enhanced treadmill endurance relative to WTs and CD47-null gastrocnemius had undergone fiber type switching to a slow twitch pattern of myoglobin and myosin heavy chain expression. In 12 month old mice, both skeletal muscle mitochondrial volume density and endurance had decreased to wild type levels. Expression of myosin heavy chain isoforms and myoglobin also reverted to a fast twitch pattern in gastrocnemius. Both CD47 and TSP1 null mice are leaner than WTs, use less oxygen and produce less heat than WT mice. CD47-null cells produce substantially less reactive oxygen species than WT cells. These data indicate that loss of signaling from the TSP1-CD47 system promotes accumulation of normally functioning mitochondria in a tissue-specific and age-dependent fashion leading to enhanced physical performance, lower reactive oxygen species production and more efficient metabolism.
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影响因子：
2.8
作者：
Corsetti, Giovanni;Pasini, Evasio;Bianchi, Rossella
通讯作者：
Bianchi, Rossella
影响因子：
4.8
作者：
Frazier, WA;Gao, AG;Linder, ME
通讯作者：
Linder, ME
影响因子：
20.1
作者：
Isenberg, Jeff S.;Romeo, Martin J.;Roberts, David D.
通讯作者：
Roberts, David D.
DOI：
10.1016/j.matbio.2009.01.002
发表时间：
2009-03
期刊：
Matrix biology : journal of the International Society for Matrix Biology
影响因子：
--
作者：
Isenberg JS;Qin Y;Maxhimer JB;Sipes JM;Despres D;Schnermann J;Frazier WA;Roberts DD
通讯作者：
Roberts DD
影响因子：
9
作者：
Isenberg, Jeff S.;Pappan, Loretta K.;Roberts, David D.
通讯作者：
Roberts, David D.