DIFFERENCES IN THE GLUTATHIONE SYSTEM OF CULTURED AORTIC SMOOTH-MUSCLE CELLS FROM YOUNG AND AGED RATS
DIFFERENCES IN THE GLUTATHIONE SYSTEM OF CULTURED AORTIC SMOOTH-MUSCLE CELLS FROM YOUNG AND AGED RATS
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DOI：
10.1016/0021-9150(93)90200-e
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发表时间：
1993-05-01
期刊：
影响因子：
5.3
通讯作者：
POGGI, A
中科院分区：
文献类型：
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作者：
PORRECA, E;DIFEBBO, C;POGGI, A
本实验以4-6周龄（青年）和15月龄（老年）大鼠胸主动脉平滑肌细胞（SMC）为模型，研究了谷胱甘肽（GSH）系统与细胞增殖的关系。与年轻大鼠的细胞相比，老年大鼠的SMC显示出更高水平的总非蛋白巯基化合物（T-SH），谷胱甘肽转移酶（GST）和谷胱甘肽还原酶（GSSG-Red）活性增加。这些变化与老年大鼠SMC增殖率增加有关。为了更好地评估GSH对细胞增殖的作用，使用γ-谷氨酰-半胱氨酸合成酶的特异性抑制剂DL-丁硫氨酸-SR-磺酰亚胺（BSO）。BSO显示出对细胞生长的剂量依赖性抑制，孵育48-72小时后，IC 50为10（-4）M。去除BSO恢复细胞生长，进一步表明GSH水平和血管细胞增殖之间的联系。BSO对青年大鼠平滑肌细胞的抑制作用约为老年大鼠平滑肌细胞的2倍。BSO对青年大鼠SMC增殖抑制率为56%，对老年大鼠SMC增殖抑制率为32%（10（-4）M，孵育72 h）。观察到年轻和老年大鼠SMC的GSH水平分别平行降低38%和19%，表明年龄相关因素可能影响GSH系统参与细胞增殖。
We studied the relation between the glutathione (GSH) system and cell proliferation in a model of smooth muscle cells (SMC) derived from the thoracic aorta of 4-6-week-old (young) and 15-month-old (aged) rats. SMC from aged rats showed greater levels of total non-protein thiol compounds (T-SH), increased glutathione transferase (GST) and increased glutathione reductase (GSSG-Red) activities compared with cells from young rats. These changes were associated with an increased proliferation rate of SMC from aged rats. To evaluate the role of GSH on cell proliferation better, a specific inhibitor of gamma-glutamyl-cystein synthetase, DL-buthionine-SR-sulphoximine (BSO) was used. BSO showed a dose-dependent inhibition of cell growth, with an IC50 of 10(-4) M, after 48-72 h of incubation. Removal of BSO restored cell growth, further suggesting a link between GSH levels and vascular cell proliferation. The inhibitory effect of BSO was about two times greater on SMC from young than on SMC from aged rats. BSO showed 56% inhibition on the proliferation of SMC from young rats and 32% inhibition on SMC from aged rats (10(-4) M, 72 h of incubation). A parallel reduction of GSH levels of 38% and 19% for SMC from young and aged rats, respectively, was observed, suggesting that age-related factors may influence the involvement of GSH system in cell proliferation.