Myofibrillar protein synthesis in myostatin-deficient mice
Myofibrillar protein synthesis in myostatin-deficient mice
复制标题
DOI：
10.1152/ajpendo.00433.2005
复制
发表时间：
2006-03-01
影响因子：
5.1
通讯作者：
Pinkert, CA
中科院分区：
文献类型：
--
作者：
Welle, S;Bhatt, K;Pinkert, CA
增加蛋白质合成或延长蛋白质半衰期是支持肌肉过度生长和肌肉肥大的维持所必需的。这个问题是通过测定系统性泛洪剂量的L-[环-H-2(5)]苯丙氨酸后，通过测量示踪剂掺入来确定结构性肌生长抑素缺乏症(MSTN(Delta E3/Delta E3))或正常表达(MSTN(+/+))小鼠的肌原纤维蛋白合成的活体速率来解决的。在5-6周龄时，与MSTN(+/+)小鼠相比，MSTN(Delta E3/Delta E3)小鼠的肌肉质量(40%)、肌原纤维合成分数(14%)和每条肌肉的蛋白质合成(60%)增加。随着成熟，合成率下降了50%，同时肌肉中DNA和RNA[总、28S rRNA和聚(A)RNA]浓度也降低了。6mo龄时，与MSTN(+/+)相比，MSTN(Delta E3/Delta E3)小鼠的肌肉质量(90%)和单肌肌原纤维合成(85%)的增加幅度更大，但合成率正常。估计的肌原纤维蛋白半衰期不受肌抑制素缺乏的影响。年轻和成熟的MSTN(Delta E3/Delta E3)小鼠肌肉DNA含量均降低，而RNA含量正常，因此MSTN(Delta E3/Delta E3)小鼠的RNA/DNA比正常高约30%。因此，肌肉生长抑素缺陷小鼠每块肌肉的蛋白质合成和RNA含量的增加不能完全用肌核数量的增加来解释。
Either increased protein synthesis or prolonged protein half-life is necessary to support the excessive muscle growth and maintenance of enlarged muscles in myostatin-deficient mice. This issue was addressed by determining in vivo rates of myofibrillar protein synthesis in mice with constitutive myostatin deficiency ( Mstn(Delta E3/Delta E3)) or normal myostatin expression ( Mstn(+/+)) by measuring tracer incorporation after a systemic flooding dose of L-[ ring-H-2(5)] phenylalanine. At 5 - 6 wk of age, Mstn(Delta E3/Delta E3) mice had increased muscle mass ( 40%), fractional rates of myofibrillar synthesis ( 14%), and protein synthesis per whole muscle ( 60%) relative to Mstn(+/+) mice. With maturation, fractional rates of synthesis declined > 50% in parallel with decreased DNA and RNA [ total, 28S rRNA, and poly( A) RNA] concentrations in muscle. At 6 mo of age, Mstn(Delta E3/Delta E3) mice had even greater increases in muscle mass ( 90%) and myofibrillar synthesis per muscle ( 85%) relative to Mstn(+/+) mice, but the fractional rate of synthesis was normal. Estimated myofibrillar protein half-life was not affected by myostatin deficiency. Muscle DNA concentrations were reduced in both young and mature Mstn(Delta E3/Delta E3) mice, whereas RNA concentrations were normal, so the ratio of RNA to DNA was similar to 30% greater than normal in Mstn(Delta E3/Delta E3) mice. Thus the increased protein synthesis and RNA content per muscle in myostatin-deficient mice cannot be explained entirely by an increased number of myonuclei.