The role of zinc in growth and cell proliferation
The role of zinc in growth and cell proliferation
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DOI：
10.1093/jn/130.5.1500s
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发表时间：
2000-05-01
影响因子：
4.2
通讯作者：
MacDonald, RS
中科院分区：
文献类型：
--
作者：
MacDonald, RS
生长抑制是缺锌的主要症状。在饲喂锌不足的饮食中，动物的食物摄入量和生长在4-5天内都会减少，尽管食物摄入量和生长同时减少，但能量摄入的减少并不是生长的限制因素，因为强制饲喂动物锌不足的饮食无法维持生长。因此，食物摄入和生长似乎是通过独立但协调良好的机制受到锌的调节。尽管对锌代谢进行了长期研究，但锌在细胞增殖中的首要限制作用仍不清楚。锌以多种方式参与细胞增殖的调节；它对于影响细胞分裂和增殖的酶系统至关重要。从细胞外环境中去除锌会导致脱氧胸苷激酶活性降低和腺苷(5')四磷酸(5')-腺苷水平降低。因此，锌可以通过这些系统直接调节 DNA 合成。锌还影响细胞分裂的激素调节。具体来说，垂体生长激素 (GH) 胰岛素样生长因子-I (IGF-I) 轴对锌状态有反应。在缺锌情况下，尽管循环 IGF-I 浓度持续降低，但已观察到 GH 循环浓度升高和降低。然而，通过外源给药维持 GH 或 IGF-I 水平并不能逆转生长失败，这表明激素信号传导存在缺陷，锌似乎对于 IGF-I 诱导细胞增殖至关重要；调节位点是受体后结合。总体而言，证据表明，锌可用性的降低会影响膜信号系统和细胞内第二信使，从而协调细胞增殖以响应 IGF-I。
The inhibition of growth is a cardinal symptom of zinc deficiency. In animals fed a zinc-inadequate diet, both food intake and growth are reduced within 4-5 d, Despite the concomitant reduction in food intake and growth, reduced energy intake is not the limiting factor in growth, because force-feeding a zinc-inadequate diet to animals fails to maintain growth. Hence, food intake and growth appear to be regulated by zinc through independent, although well coordinated, mechanisms. Despite the long-term study of zinc metabolism, the first limiting role of zinc in cell proliferation remains undefined. Zinc participates in the regulation of cell proliferation in several ways; it is essential to enzyme systems that influence cell division and proliferation. Removing zinc from the extracellular milieu results in decreased activity of deoxythymidine kinase and reduced levels of adenosine(5')tetraphosphate(5')-adenosine. Hence, zinc may directly regulate DNA synthesis through these systems. Zinc also influences hormonal regulation of cell division. Specifically, the pituitary growth hormone (GH)insulin-like growth factor-I (IGF-I) axis is responsive to zinc status, Both increased and decreased circulating concentrations of GH have been observed in zinc deficiency, although circulating IGF-I concentrations are consistently decreased. However, growth failure is not reversed by maintaining either GH or IGF-I levels through exogenous administration, which suggests the defect occurs in hormone signaling, Zinc appears to be essential for IGF-I induction of cell proliferation; the site of regulation is postreceptor binding. Overall, the evidence suggests that reduced zinc availability affects membrane signaling systems and intracellular second messengers that coordinate cell proliferation in response to IGF-I.