HIGH GLUCOSE PROLONGS CELL-CYCLE TRAVERSAL OF CULTURED HUMAN-ENDOTHELIAL CELLS
HIGH GLUCOSE PROLONGS CELL-CYCLE TRAVERSAL OF CULTURED HUMAN-ENDOTHELIAL CELLS
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DOI：
10.2337/diabetes.36.11.1261
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发表时间：
1987-11-01
期刊：
影响因子：
7.7
通讯作者：
TOLEDO, S
中科院分区：
文献类型：
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作者：
LORENZI, M;NORDBERG, JA;TOLEDO, S
有证据表明糖尿病状态会对某些细胞群的复制产生不利影响。我们发现，暴露于高环境葡萄糖 (20 mM) 会导致原代培养物中人内皮细胞细胞周期各个阶段的延迟。 S期细胞用溴脱氧尿苷（胸苷类似物）标记，并通过流式细胞术在连续时间点分析标记群体的细胞周期位置。暴露于高葡萄糖 7-8 天的细胞在 S 期和 G2 期的运动均受到延迟，因此 24 小时内溴脱氧尿苷阳性细胞的增加为 1.6 倍，而对照培养物为 2.0 倍。在使用长春花碱抑制有丝分裂来研究细胞脱离 G1 期而不受重新进入细胞干扰的实验中，在高葡萄糖条件下生长的培养物中，G1 区室的消耗被显着抑制。慢性高血糖对细胞周期产生影响，但总蛋白质合成并未减少。急性暴露于高葡萄糖对细胞周期遍历或细胞生成时间没有影响。本研究中观察到的细胞周期异常可能与我们之前在暴露于高葡萄糖的内皮细胞中观察到的 DNA 损伤有关，如果在体内发生，可能对糖尿病的血管病变和致畸性具有重要的发病机制。
There is evidence suggesting that the diabetic state adversely affects replication of certain cell populations. We document that exposure to high ambient glucose (20 mM) induces delay in various phases of the cell cycle of human endothelial cells in primary culture. Cells in S phase were labeled with bromodeoxyuridine (an analogue of thymidine), and the cell-cycle position of the labeled cohort was analyzed by flow cytometry at successive time points. The movement of cells exposed to high glucose for 7-8 days was retarded both in S and G2 phases so that the increase in bromodeoxyuridine-positive cells over 24 h was 1.6-fold, versus 2.0-fold in control cultures. In experiments in which mitotic arrest with vinblastine was used to investigate the movement of cells out of G1 phase without interference from reentering cells, depletion of the G1 compartment was significantly inhibited in cultures grown in high glucose. The effects of chronic high glucose on cell cycle occurred while total protein synthesis was not diminished. Acute exposure to high glucose had no effect on cell-cycle traversal or cell generation time. Cell-cycle abnormalities observed in this study may relate to the DNA damage we have previously observed in endothelial cells exposed to high glucose and, if occurring in vivo, could be of pathogenetic importance for the vascular lesions and teratogenicity of diabetes.