Department of Biochemistry and Molecular Biology "Ernesto Quagliariello", University of Bari, Bari, Italy.
Biofactors. 2010 Jan-Feb;36(1):70-7. doi: 10.1002/biof.74.
The effect of acetyl-L-carnitine (ALCAR) supplementation to 3-month-old rats in normal-loading and unloading conditions has been here investigated by a combined morphological, biochemical and transcriptional approach to test whether ALCAR might cause a remodeling of the metabolic/contractile phenotype of soleus muscle. Morphological assessment demonstrated an increase of type I oxidative fiber content and cross-sectional area in ALCAR-treated animals both in normal-loading and in unloading conditions. ALCAR prevented loss of mitochondrial mass in unloaded animals whereas no ALCAR-dependent increase of mitochondrial mass occurred in normal-loaded muscle. Validated microarray analysis delineated an ALCAR-induced maintenance of a slow-oxidative expression program only in unloaded soleus muscle. Indeed, the muscle adjustment of the expression profile of factors underlying mitochondrial oxidative metabolism, protein turnover, fiber type differentiation and an adaptation of voltage-gated ion channel expression was distinguishable with respect to the loading status. This selectivity may suggest a key role of muscle loading status in the manifestation of ALCAR effects. The results extend to a broader level of biological informations the previous notion on ALCAR positive effect in rat soleus muscle during unloading and point to a role of ALCAR for the maintenance of its slow-oxidative fiber character.
本研究采用形态学、生物化学和转录组学相结合的方法，探讨了乙酰左旋肉碱（ALCAR）在正常负荷和去负荷条件下对 3 月龄大鼠的影响，以检验 ALCAR 是否可能引起比目鱼肌代谢/收缩表型的重塑。形态学评估表明，在正常负荷和去负荷条件下，ALCAR 处理的动物的 I 型氧化纤维含量和横截面积增加。ALCAR 防止了去负荷动物中线粒体质量的丧失，而在正常负荷的肌肉中，线粒体质量没有增加。经验证的微阵列分析表明，ALCAR 仅在去负荷的比目鱼肌中维持缓慢氧化的表达程序。事实上，肌肉对线粒体氧化代谢、蛋白周转、纤维类型分化以及电压门控离子通道表达的适应相关因素的表达谱的调整可以根据负荷状态来区分。这种选择性可能表明肌肉负荷状态在 ALCAR 作用表现中的关键作用。这些结果将 ALCAR 在去负荷大鼠比目鱼肌中的积极作用的先前概念扩展到更广泛的生物学信息层面，并指出 ALCAR 对于维持其缓慢氧化纤维特征的作用。
