Effect of daptomycin on primary rat muscle cell cultures in vitro
Effect of daptomycin on primary rat muscle cell cultures in vitro
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DOI：
10.1007/s11626-010-9311-5
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发表时间：
2010-07-01
影响因子：
2.1
通讯作者：
Larkin, Lisa M.
中科院分区：
文献类型：
--
作者：
Kostrominova, Tatiana Y.;Coleman, Scott;Larkin, Lisa M.
达托霉素是一种脂肽类抗生素，对革兰氏阳性细菌具有很强的杀菌活性，以前报道过对骨骼肌有轻微的副作用。本研究旨在通过使用大鼠肌肉原代培养物进一步表征达托霉素对骨骼肌的影响。我们的研究表明，达托霉素对分化的、自发收缩的大鼠肌管原代培养的质膜具有浓度依赖性和时间依赖性。即使在最高的达托霉素浓度（6,000 A μ g/mL）下，培养物中未分化的成肌细胞或其他单核细胞也没有明显的影响。在达托霉素浓度为2000 a μ g/mL的培养基中，20-30%的分化肌管出现质膜损伤；浓度在1000 μ g/mL及以下时未见肌管损伤。在750 A μ g/mL时，肌管自发性收缩的短暂丧失是明显的，而在2000 A μ g/mL及以上时，观察到自发性收缩的永久性丧失。这些结果提示，达托霉素对骨骼肌作用的可能靶点是高分化肌管质膜上的结构。
Daptomycin is a lipopeptide antibiotic that has strong bactericidal activity against Gram-positive bacteria and that was previously reported to exhibit minor side effects on skeletal muscle. This study was designed to further characterize the effect of daptomycin on skeletal muscle through the use of primary cultures of muscles from rats. Our investigations demonstrated that daptomycin has a concentration-dependent and time-dependent effect on the plasma membrane of primary cultures of differentiated, spontaneously contracting rat myotubes. No effects were evident in non-differentiated myoblasts or other mononucleated cells present in cultures even at the highest daptomycin concentrations tested (6,000 A mu g/mL). In cultures treated with daptomycin at a concentration of 2,000 A mu g/mL, plasma membrane damage was observed in similar to 20-30% of differentiated myotubes; no myotube damage was detected at concentrations of 1,000 A mu g/mL and below. A transient loss of spontaneous myotube contractions was evident at 750 A mu g/mL, while at 2,000 A mu g/mL and above, a permanent loss of spontaneous contractility was observed. These results suggest that the putative targets for daptomycin effects on skeletal muscle are structures on the plasma membrane of highly differentiated myotubes.