Reduced cell replication and induction of apoptosis by advanced glycation end products in rat Schwann cells
Reduced cell replication and induction of apoptosis by advanced glycation end products in rat Schwann cells
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DOI：
10.1016/j.bbrc.2004.05.159
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发表时间：
2004-07-16
影响因子：
3.1
通讯作者：
Yagihashi, S
中科院分区：
文献类型：
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作者：
Sekido, H;Suzuki, T;Yagihashi, S
我们研究了来自葡萄糖、甘油醛和乙醇醛的晚期糖基化终产物（AGE）（分别命名为AGE-1、AGE-2和AGE-3）对培养的雪旺细胞活力、复制率和细胞因子产生的影响。AGE-2和AGE-3诱导细胞凋亡，MTT法检测细胞存活率显著降低，而AGE-1不诱导细胞凋亡。抗氧化剂α-硫辛酸完全阻止了这种下降，p38丝裂原活化蛋白激酶抑制剂SB 202190部分阻止了这种下降。AGE-2和AGE-3可引起线粒体膜电位降低。此外，AGE-2和AGE-3显著抑制复制率，如溴脱氧尿苷摄取减少所示，而它们增强TNF-α和IL-1 β向培养基中的释放并激活核因子-κ B。AGE-1对这些指标的影响是不明确的。AGE-2和AGE-3引起的一系列事件可能是糖尿病神经病变患者发病机制的某些方面。(C)2004年爱思唯尔公司All rights reserved.
We investigated the effects of advanced glycation end products (AGEs) derived from glucose, glyceraldehyde, and glycolaldehyde (designated as AGE-1, -2, and -3, respectively) on the viability, replication rate, and cytokine production of cultured Schwann cells. AGE-2 and -3, but not AGE-1, induced apoptosis, and significantly decreased the viability measured by MTT assay. The decrease was prevented completely by antioxidant a-lipoic acid and was prevented partially by p38 mitogen-activated protein kinase inhibitor SB202190. The decrease in mitochondrial membrane potential by AGE-2 and -3 was also observed. In addition, AGE-2 and -3 significantly suppressed the replication rate as shown by reduced bromodeoxyuridine uptake, whereas they enhanced the release of TNF-alpha and IL-1beta into the medium and activated nuclear factor-kappaB. The effects of AGE-1 on these measures were equivocal. The series of events elicited by AGE-2 and -3 may be responsible for some of the aspects of pathogenetic mechanisms in patients with diabetic neuropathy. (C) 2004 Elsevier Inc. All rights reserved.