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H9c2 成肌细胞分化过程中的代谢重塑:与体外毒性研究的相关性。

Metabolic remodeling during H9c2 myoblast differentiation: relevance for in vitro toxicity studies.

机构信息

Center for Neuroscience and Cell Biology, University of Coimbra, Portugal.

出版信息

Cardiovasc Toxicol. 2011 Jun;11(2):180-90. doi: 10.1007/s12012-011-9112-4.

DOI:10.1007/s12012-011-9112-4
PMID:21431998
Abstract

H9c2 cells, derived from the ventricular part of an E13 BDIX rat heart, possess a proliferative and relatively undifferentiated phenotype but can be readily directed to differentiate under reduced serum conditions originating cells presenting muscle features. Skeletal or cardiac phenotypes can be originated depending on whether or not serum reduction is accompanied by a daily treatment with all-trans-retinoic acid. In the present study, we aimed to characterize and compare the metabolic profile of H9c2 cells at various differentiation states, correlating the differences between different populations with muscle-specific development. We determined that H9c2 myoblasts remodel their metabolism upon differentiation, with undifferentiated cells more reliant on glycolysis, as demonstrated by higher lactate production rates. Differentiated cells adopted a more oxidative metabolism with better coupling between the glycolytic and oxidative pathways, which is indicative of a metabolic evolvement toward a higher energetic efficiency state. Our findings emphasize the metabolic differences between differentiated and undifferentiated H9c2 cells and raise caution on how to adequately select the H9c2 differentiation state that will act as the better model for the design of experimental studies.

摘要

H9c2 细胞源自 E13 BDIX 大鼠心脏的心室部分,具有增殖和相对未分化的表型,但在低血清条件下很容易被诱导分化,产生具有肌肉特征的细胞。根据是否伴随全反式视黄酸的每日处理,可产生骨骼肌或心肌表型。在本研究中,我们旨在描述和比较不同分化状态下 H9c2 细胞的代谢特征,并将不同群体之间的差异与肌肉特异性发育相关联。我们发现 H9c2 成肌细胞在分化过程中重塑其代谢,未分化细胞更依赖糖酵解,这表现为更高的乳酸生成率。分化细胞采用更氧化的代谢,糖酵解和氧化途径之间的偶联更好,这表明代谢向更高能量效率状态的演变。我们的研究结果强调了分化和未分化 H9c2 细胞之间的代谢差异,并提醒人们注意如何正确选择 H9c2 分化状态,以作为设计实验研究的更好模型。

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