Advanced glycation endproducts increase EPC apoptosis and decrease nitric oxide release via MAPK pathways.
Advanced glycation endproducts increase EPC apoptosis and decrease nitric oxide release via MAPK pathways.
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晚期糖基化终产物通过 MAPK 途径增加 EPC 凋亡并减少一氧化氮释放。
DOI：
10.1016/j.biopha.2009.03.002
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发表时间：
2010
影响因子：
7.5
通讯作者：
沈成兴
中科院分区：
文献类型：
--
作者：
沈成兴
研究表明晚期糖基化终产物（Advanced Glycation Endproducts，AGE）可诱导内皮祖细胞（Endothelial Progenitor Cells，EPC）凋亡，参与糖尿病的发病机制。一氧化氮（NO）信号转导与细胞凋亡密切相关。方法将正常人EPC分别与不同浓度的AGE（0、2、20和200 mg/L）共同培养0、24、48和72 h，同时加入或不加入MAPK（ERK/P38/JNK）抑制剂。流式细胞仪检测EPC凋亡及培养上清中NO含量。RT-PCR检测内皮细胞eNOS、考克斯-2、Bcl-2和Bax的mRNA水平，Western blot检测NF-κB和Caspase-3的蛋白表达。NF-κB和Caspase-3表达呈时间依赖性（均P<0.05）。MAPK（ERK/P38/JNK）抑制剂预处理可明显抑制上述变化（P<0.05）。结论SAGE可通过MAPK途径促进EPC凋亡，减少NO释放。
OBJECTIVEPrevious studies have shown that advanced glycation endproducts (AGE) can induce endothelial progenitor cells (EPC) apoptosis, which contributes to the pathogenesis of diabetes mellitus. Nitric oxide (NO) signaling is closely associated with apoptosis. We therefore investigated the effects of AGE on human EPC apoptosis, NO release and related signal transduction pathways.METHODSEPC isolated from healthy human subjects were cultured with various concentrations of AGE (0, 2, 20 and 200mg/L) for 0, 24, 48 and 72h in the presence or absence of various MAPK (ERK/P38/JNK) inhibitors, respectively. EPC apoptosis (detected by flow cytometric analyses) and NO concentration in culture supernatant were determined. The mRNA levels of eNOS, COX-2, Bcl-2 and Bax were assessed by RT-PCR and the protein expressions of NF-κB and Caspase-3 assessed by Western blot.RESULTSIncreased EPC apoptosis and reduced NO release were induced by 200mg/L AGE, accompanied by a downregulation of eNOS and Bcl-2 expressions as well as an elevation in COX-2, Bax, NF-κB and Caspase-3 expressions in a time-dependent manner (all P<0.05). These changes were significantly attenuated by pretreatment with various MAPK (ERK/P38/JNK) inhibitors (P<0.05).CONCLUSIONSAGE can promote EPC apoptosis and decrease NO release via MAPK pathways.
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影响因子：
56.9
作者：
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影响因子：
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DOI：
10.1161/atvbaha.108.179663
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DOI：
10.1007/978-3-540-33177-3_23
发表时间：
2008
期刊：
--
影响因子：
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作者：
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通讯作者：
S. Wedge;J. Jürgensmeier
DOI：
10.1016/s0021-9258(17)36966-1
发表时间：
1994-04
期刊：
The Journal of biological chemistry
影响因子：
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Shi Du YanS;A. Schmidt;Mark Anderson;Jinghua Zhang;J. Brett;Y. Zou;D. Pinsky;David SternSn
通讯作者：
Shi Du YanS;A. Schmidt;Mark Anderson;Jinghua Zhang;J. Brett;Y. Zou;D. Pinsky;David SternSn