Inhibition of Cardiomyogenesis in Embryocarcinoma Cells Induced by Long-Term High Level of Glucose
Inhibition of Cardiomyogenesis in Embryocarcinoma Cells Induced by Long-Term High Level of Glucose
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长期高糖对胚胎癌细胞心肌生成的抑制作用
DOI：
10.1159/000445563
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发表时间：
2016-05
影响因子：
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通讯作者：
Wenjuan Li;Qianqian Guo;L. Gharibeh;Rang Xu;Sun Chen;K. Sun
中科院分区：
文献类型：
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作者：
Wenjuan Li;Qianqian Guo;L. Gharibeh;Rang Xu;Sun Chen;K. Sun
背景/目标：心肌细胞是哺乳动物心脏形成过程中最早分化的细胞类型，具有自发和有节奏地搏动的能力。高血压是妊娠前糖尿病（PGDM）心血管疾病的主要危险因素。然而，高血糖对心脏祖细胞或前体细胞分化的影响仍然知之甚少。本研究的目的是探讨高血糖是否影响胚胎癌细胞的心肌发生。研究方法：在正常葡萄糖（5.6 mmol/L）和高葡萄糖（20 mmol/L或40 mmol/L）条件下，观察1%DMSO对P19 CL 6细胞的诱导分化作用。为了探讨长期高水平葡萄糖对心肌细胞分化的影响，采用qRT-PCR分析、蛋白质印迹和免疫荧光技术检测了肌节α-辅肌动蛋白、过氧化物酶体增殖物激活受体辅激活因子-1（PGC-1α）、转录因子GATA 4和Nkx2.5的表达。结果：长期高浓度葡萄糖可明显抑制P19 CL 6细胞向心肌细胞的分化。20 mmol/L或40 mmol/L葡萄糖暴露后PGC-1α表达的变化与心肌肌球蛋白表达的变化一致。另一方面，高水平的葡萄糖浓度显著降低GATA 4和Nkx 2 -5的表达，从分化后第6天到第12天，这是由1%DMSO诱导的。结论：我们的研究结果阐明了心脏祖细胞长期暴露于高水平葡萄糖所产生的效应与GATA 4和Nkx2.5的表达降低有关，提供了一种新的机制，通过这种机制，高葡萄糖能够影响细胞分化。
Background/Aims: Cardiac myocytes constitute the first differentiated cell type during mammalian heart formation with the ability to beat spontaneously and rhythmically. Hyperglycemia is a primary risk factor for cardiovascular disease in pre-gestational diabetes mellitus (PGDM). However, the impact that hyperglycemia has on cardiac progenitors or on precursors differentiation remains poorly understood. The aim of the present study is to investigate whether hyperglycemia affects cardiomyogenesis of embryocarcinoma cells. Methods: P19CL6 cells differentiation induced by 1% DMSO was evaluated under either normal glucose (5.6 mmol/L) or high level of glucose concentrations (20 mmol/L or 40 mmol/L). To investigate the effect of long-term high level of glucose on cardiomyocytes differentiation, sarcomeric α-actinin, peroxisome proliferator-activated receptor coactivator-1 (PGC-1α), transcription factor GATA4 and Nkx2.5 were assessed by qRT-PCR analysis, western blot and immunofluorescence. Results: We observed that long-term high level of glucose markedly reduced P19CL6 cells differentiation into cardiomyocytes. The change in PGC-1α expression was consistent with changes in cardiac muscle myosin expression after exposure to 20 mmol/L or 40 mmol/L of glucose. On the other hand, the high level of glucose concentration profoundly decreased both GATA4 and Nkx2-5 expressions from day 6 to day 12 after differentiation, which was induced by 1% DMSO. Conclusion: Our results elucidate that the effect resulting from the long-term exposure of cardiac progenitors to high level of glucose is associated with decreased expression of GATA4 and Nkx2.5, providing a novel mechanism by which high glucose is able to affect cell differentiation.