Intracellular Toxic Advanced Glycation End-Products May Induce Cell Death and Suppress Cardiac Fibroblasts.
Intracellular Toxic Advanced Glycation End-Products May Induce Cell Death and Suppress Cardiac Fibroblasts.
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细胞内毒性晚期糖基化终产物可诱导细胞死亡并抑制心脏成纤维细胞。
DOI：
10.3390/metabo12070615
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发表时间：
2022-07-01
期刊：
影响因子：
4.1
通讯作者：
中科院分区：
文献类型：
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作者：
心血管疾病（CVD）是一种由心肌细胞功能障碍和细胞死亡引起的生活方式相关疾病（LSRD）。心肌成纤维细胞受到特定信号的激活和分化，如损伤心肌细胞释放的转化生长因子-β，对心肌细胞的保护、心脏组织修复和重塑至关重要。相反，心脏成纤维细胞已被证明可诱导心肌细胞损伤或死亡，并与心脏肥厚等疾病的发病机制有关。由于其细胞毒性和与LSRD的相关性，我们将甘油醛衍生的晚期糖基化终产物（AGEs）称为毒性AGEs （TAGE）。在心肌缺血情况下，细胞内TAGE降低心肌细胞的搏动率，诱导细胞死亡。CVD患者血液中TAGE水平升高，与心肌缺血相关，体外血管内皮细胞发生动脉粥样硬化的风险增加。心脏成纤维细胞功能障碍或细胞死亡与某些器官分泌的细胞内和细胞外TAGE之间的关系尚不清楚。我们通过槽点印迹分析检测了细胞内TAGE的细胞毒性，并在正常人心脏成纤维细胞（HCF）中检测了TAGE修饰的牛血清白蛋白（TAGE- bsa），这是细胞外TAGE的一种模型。在正常HCF中，细胞内TAGE诱导细胞死亡，而TAGE- bsa即使在异常高的非生理水平下也不会。因此，生理条件下仅细胞内TAGE诱导HCF细胞死亡，可能抑制了HCF的作用。
Cardiovascular disease (CVD) is a lifestyle-related disease (LSRD) induced by the dysfunction and cell death of cardiomyocytes. Cardiac fibroblasts are activated and differentiate in response to specific signals, such as transforming growth factor-β released from injured cardiomyocytes, and are crucial for the protection of cardiomyocytes, cardiac tissue repair, and remodeling. In contrast, cardiac fibroblasts have been shown to induce injury or death of cardiomyocytes and are implicated in the pathogenesis of diseases such as cardiac hypertrophy. We designated glyceraldehyde-derived advanced glycation end-products (AGEs) as toxic AGEs (TAGE) due to their cytotoxicity and association with LSRD. Intracellular TAGE in cardiomyocytes decreased their beating rate and induced cell death in the absence of myocardial ischemia. The TAGE levels in blood were elevated in patients with CVD and were associated with myocardial ischemia along with increased risk of atherosclerosis in vascular endothelial cells in vitro. The relationships between the dysfunction or cell death of cardiac fibroblasts and intracellular and extracellular TAGE, which are secreted from certain organs, remain unclear. We examined the cytotoxicity of intracellular TAGE by a slot blot analysis, and TAGE-modified bovine serum albumin (TAGE-BSA), a model of extracellular TAGE, in normal human cardiac fibroblasts (HCF). Intracellular TAGE induced cell death in normal HCF, whereas TAGE-BSA did not, even at aberrantly high non-physiological levels. Therefore, only intracellular TAGE induced cell death in HCF under physiological conditions, possibly inhibiting the role of HCF.
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影响因子：
5.9
作者：
Nasu R;Furukawa A;Suzuki K;Takeuchi M;Koriyama Y
通讯作者：
Koriyama Y
影响因子：
4.8
作者：
Burke RM;Burgos Villar KN;Small EM
通讯作者：
Small EM
影响因子：
4.1
作者：
Vang, Shia;Cochran, Phillip;Sebastian Domingo, Julio;Krick, Stefanie;Barnes, Jarrod Wesley
通讯作者：
Barnes, Jarrod Wesley
影响因子：
--
作者：
Ramasamy R;Schmidt AM
通讯作者：
Schmidt AM
血清毒性时代水平（Tage）可能是与生活方式相关疾病的发作/进展的有前途的新型生物标志物。
DOI：
10.3390/diagnostics6020023
发表时间：
2016-06-07
期刊：
Diagnostics (Basel, Switzerland)
影响因子：
--
作者：
Takeuchi M
通讯作者：
Takeuchi M