Changes in Stress-Mediated Markers in a Human Cardiomyocyte Cell Line under Hyperglycemia.
Changes in Stress-Mediated Markers in a Human Cardiomyocyte Cell Line under Hyperglycemia.
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DOI：
10.3390/ijms221910802
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发表时间：
2021-10-07
影响因子：
5.6
通讯作者：
Chattopadhyay M
中科院分区：
文献类型：
--
作者：
Thakur V;Alcoreza N;Cazares J;Chattopadhyay M
糖尿病是心血管疾病，尤其是心肌病的主要危险因素，心肌病是一种心脏平滑肌变厚变硬的疾病，影响心脏收缩细胞心肌细胞的功能。随着时间的推移，不受控制的血糖水平升高会导致氧化应激，从而导致炎症和表观遗传机制的改变。在当前的研究中，我们研究了高血糖是否可以通过直接影响心肌细胞的这些变化来改变心功能。为了评估高葡萄糖的不良影响，我们测量了间隙连接蛋白、连接蛋白43的水平，连接蛋白43负责调节心脏电活动和肌钙蛋白I，肌钙蛋白I是心肌肌钙蛋白复合物的一部分，通常被用作缺血性心脏病的心脏标志物。本研究使用AC16人心肌细胞。在高血糖条件下，暴露24小时后，这些细胞显示出连接蛋白43和肌钙蛋白i水平的改变。我们还检测了高血糖诱导的表观遗传标记的变化：H3K9me1、SIRT1和组蛋白去乙酰化酶(HDAC)-2，以及炎症和应激相关介质，如热休克蛋白(HSP)-60、晚期糖基化终产物受体（RAGE）、toll样受体(TLR)-4、高迁移率组盒(HMGB)-1和CXC趋化因子受体(CXCR)-4。暴露于25mM葡萄糖的心肌细胞48 h后HSP60和SIRT1下调。我们进一步研究了高血糖介导的间隙连接蛋白CX43和CXC趋化因子受体CXCR4的降低，这可能会影响心肌细胞暴露于高糖24和48 h时的生理功能。与组蛋白甲基化标记物H3K9me1的变化一起，在暴露24小时时证明了高血糖诱导的心肌细胞损伤。我们的研究证实，24至48小时的高血糖暴露可以刺激体外心肌细胞中应激介导的炎症介质。在高血糖诱导的心肌细胞中，这些应激相关的变化可能进一步启动损伤标志物的增加，最终可能改变表观遗传过程。因此，表观遗传和炎症机制以及下游信号通路的改变可能对短期和长期暴露于高糖环境下的心肌细胞的功能有直接影响。
Diabetes is a major risk factor for cardiovascular diseases, especially cardiomyopathy, a condition in which the smooth muscles of the heart become thick and rigid, affecting the functioning of cardiomyocytes, the contractile cells of the heart. Uncontrolled elevated glucose levels over time can result in oxidative stress, which could lead to inflammation and altered epigenetic mechanisms. In the current study, we investigated whether hyperglycemia can modify cardiac function by directly affecting these changes in cardiomyocytes. To evaluate the adverse effect of high glucose, we measured the levels of gap junction protein, connexin 43, which is responsible for modulating cardiac electric activities and Troponin I, a part of the troponin complex in the heart muscles, commonly used as cardiac markers of ischemic heart disease. AC16 human cardiomyocyte cells were used in this study. Under hyperglycemic conditions, these cells demonstrated altered levels of connexin 43 and Troponin-I after 24 h of exposure. We also examined hyperglycemia induced changes in epigenetic markers: H3K9me1, Sirtuin-1 (SIRT1), and histone deacetylase (HDAC)-2 as well as in inflammatory and stress-related mediators, such as heat shock protein (HSP)-60, receptor for advanced glycation end products (RAGE), toll-like receptor (TLR)-4, high mobility group box (HMGB)-1 and CXC chemokine receptor (CXCR)-4. Cardiomyocytes exposed to 25mM glucose resulted in the downregulation of HSP60 and SIRT1 after 48 h. We further examined that hyperglycemia mediated the decrease in the gap junction protein CX43, as well as CXC chemokine receptor CXCR4 which may affect the physiological functions of the cardiomyocytes when exposed to high glucose for 24 and 48 h. Upregulated expression of DNA-binding nuclear protein HMGB1, along with changes in histone methylation marker H3K9me1 have demonstrated hyperglycemia-induced damage to cardiomyocyte at 24 h of exposure. Our study established that 24 to 48 h of hyperglycemic exposure could stimulate stress-mediated inflammatory mediators in cardiomyocytes in vitro. These stress-related changes in hyperglycemia-induced cardiomyocytes may further initiate an increase in injury markers which eventually could alter the epigenetic processes. Therefore, epigenetic and inflammatory mechanisms in conjunction with alterations in a downstream signaling pathway could have a direct effect on the functionality of the cardiomyocytes exposed to high glucose during short and long-term exposures.
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影响因子：
37.8
作者：
Tirziu D;Giordano FJ;Simons M
通讯作者：
Simons M
影响因子：
9.5
作者：
Schäfler, AE;Kirmanoglou, K;Schumacher, B
通讯作者：
Schumacher, B
影响因子：
5.7
作者：
Christensen, Dan P.;Dahllof, Mattias;Mandrup-Poulsen, Thomas
通讯作者：
Mandrup-Poulsen, Thomas
DOI：
10.1007/s00018-018-2857-1
发表时间：
2018-09
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Yerra VG;Advani A
通讯作者：
Advani A
影响因子：
20.1
作者：
Hussain, Shafaat;Khan, Abdul Waheed;Cosentino, Francesco
通讯作者：
Cosentino, Francesco