Insulin-like growth factor 1 and transforming growth factor-β stimulate cystine/glutamate exchange activity in dental pulp cells.
Insulin-like growth factor 1 and transforming growth factor-β stimulate cystine/glutamate exchange activity in dental pulp cells.
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DOI：
10.1016/j.joen.2011.03.031
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发表时间：
2011-07
影响因子：
4.2
通讯作者：
Lobner D
中科院分区：
文献类型：
--
作者：
Pauly K;Fritz K;Furey A;Lobner D
生长因子IGF-1和TGF-β对培养的牙髓细胞具有保护作用，可对抗复合材料Durafill VS和Flow Line的毒性。由于这些材料的毒性是由氧化应激介导的，因此IGF-1和TGF-β的保护作用似乎可能是通过增强内源性抗氧化机制。我们使用培养的牙髓细胞来确定IGF-1和TGF-β的保护作用的机制，重点是谷胱甘肽系统和胱氨酸/谷氨酸交换（系统xc-）的作用。我们发现，添加谷胱甘肽单乙酯可减弱Durafill VS和Flow Line的毒性，表明细胞抗氧化剂谷胱甘肽具有特定作用。支持这一假设，我们发现IGF-1和TGF-β对谷胱甘肽合成抑制剂丁硫氨酸亚砜亚胺的毒性具有保护作用。由于细胞胱氨酸水平是谷胱甘肽产生的限制因素，我们测试了IGF-1和TGF-β对胱氨酸摄取的影响。这两种生长因子均刺激系统xc介导的胱氨酸摄取。此外，它们减弱了Durafill VS和Flow Line诱导的谷胱甘肽耗竭。结果表明，IGF-1和TGF-β通过刺激系统xc介导的胱氨酸摄取，导致细胞谷胱甘肽的维持，具有保护作用。生长因子对牙髓细胞的这种新作用不仅对预防牙科材料的毒性，而且对这些细胞的一般功能具有意义。
The growth factors IGF-1 and TGF-β are protective to dental pulp cells in culture against the toxicity of the composite materials Durafill VS and Flow Line. Since the toxicity of these materials is mediated by oxidative stress, it seemed possible that the protective effects of IGF-1 and TGF-β were through enhancement of an endogenous antioxidant mechanism. We used cultured dental pulp cells to determine the mechanism of the protective effects of IGF-1 and TGF-β, focusing on the glutathione system and the role of cystine/glutamate exchange (system xc-). We found that the toxicity of Durafill VS and Flow Line was attenuated by addition of glutathione monoethylester, suggesting a specific role for the cellular antioxidant glutathione. Supporting this hypothesis we found that IGF-1 and TGF-β were protective against the toxicity of the glutathione synthesis inhibitor buthionine sulfoximine. Since levels of cellular cystine are the limiting factor in the production of glutathione we tested the effects of IGF-1 and TGF-β on cystine uptake. Both growth factors stimulated system xc- mediated cystine uptake. Furthermore, they attenuated the glutathione depletion induced by Durafill VS and Flow Line. The results suggest that IGF-1 and TGF-β are protective through the stimulation of system xc- mediated cystine uptake leading to maintenance of cellular glutathione. This novel action of growth factors on dental pulp cells has implications not only for preventing toxicity of dental materials but also for the general function of these cells.
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影响因子：
3.4
作者：
Kaur, Parvinder;Aschner, Michael;Syversen, Tore
通讯作者：
Syversen, Tore
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Lobner, D
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Lobner, D
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