Differential antioxidant enzyme activities and glutathione content between rat and rabbit conceptuses
Differential antioxidant enzyme activities and glutathione content between rat and rabbit conceptuses
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DOI：
10.1016/s0891-5849(01)00502-0
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发表时间：
2001-05-15
影响因子：
7.4
通讯作者：
Harris, C
中科院分区：
文献类型：
--
作者：
Hansen, JM;Choe, HS;Harris, C
氧化还原状态调节许多细胞过程，如转录因子激活和结合、蛋白质折叠和钙隔离。由于细胞中最丰富的还原当量是谷胱甘肽 (GSH)，因此它可能对致畸剂发挥作用，从而导致氧化应激并破坏参与分化和增殖的途径。对已证明对致畸剂具有不同敏感性的两个物种的氧化还原状态的研究代表了确定氧化还原改变在致畸中的作用的新方法。此外，检查胚胎的特定区域也可能有助于解释为什么某些组织特别敏感，而其他组织对氧化损伤具有抵抗力。在本研究中，新西兰白兔 (GD 12) 和 Sprague Dawley 大鼠胚胎 (GD 13) 在相似发育的日子里从子宫中取出。每个胚胎被解剖成三部分——四肢、头部和躯干。将样品置于适当的缓冲液中，用于测量直接和间接氧化还原状态贡献者 - 谷胱甘肽、半胱氨酸、硫氧还蛋白、谷胱甘肽二硫化物、蛋白质-谷胱甘肽混合二硫化物、超氧化物歧化酶、谷胱甘肽过氧化物酶和谷胱甘肽二硫化物还原酶。整个胚胎的物种比较表明，兔胚胎比大鼠胚胎具有更高的氧化还原电位（氧化性更强）。总的来说，研究结果表明，兔子可能对改变氧化还原的致畸剂更敏感，因为它本质上更促氧化，并且可能更容易受到干扰，导致细胞过程的失调。与胚胎头部和躯干相比，肢体中的差异最为明显，兔子肢体比大鼠肢体具有显着更强的促氧化氧化还原环境。像这样的物种比较可能有助于理解氧化还原位移如何影响细胞过程，并有助于调节可能与致畸机制相关的生化和分子事件。这些可能有助于为选择研究物种提供更完整的理由，并提供与人类发育毒物更好的相关性。 (C) 2001 爱思唯尔科学公司。
Redox status regulates numerous cellular processes like transcription factor activation and binding, protein folding, and calcium sequestration. Because the most abundant reducing equivalent in the cell is glutathione (GSH), it could play a role for teratogens that cause oxidative stress and disrupt pathways involved in differentiation and proliferation. Investigation of the redox status of two species that have demonstrated differential sensitivity to teratogens represents a novel approach for determining the role of redox alteration in teratogenesis. Furthermore, examining specific regions of the embryo may also help to explain why certain tissues are uniquely sensitive, while others are resistant to oxidative insult. In the presented study, New Zealand White rabbit (GD 12) and Sprague Dawley rat embryos (GD 13) were removed from the uterus on days of similar development. Each embryo was dissected into three portions-the limbs, the head, and the trunk. Samples were placed in the appropriate buffers for the measurement of both direct and indirect redox status contributors-GSH, cysteine, thioredoxin, glutathione disulfide, protein-glutathione mixed disulfides, superoxide dismutase, glutathione peroxidase, and glutathione disulfide reductase. Species comparison of whole embryos indicated that the rabbit embryo possesses a higher redox potential (more oxidative) than the rat embryo. Findings, in general, show that the rabbit may be more sensitive to redox-altering teratogens because it is inherently more pro-oxidizing and may be more easily perturbed resulting in misregulation of cellular processes. Differences were most apparent in the limb as compared to the embryonic head and trunk, where the rabbit limb has a significantly more pro-oxidizing redox environment than the rat limb. Species comparisons like these may help in the understanding of how redox shifts affect cellular processes and would contribute to regulation of biochemical and molecular events that may be associated with mechanisms of teratogenesis. These may contribute to a more complete rationale for choosing a species for study and provide a better correlation with human developmental toxicants. (C) 2001 Elsevier Science Inc.