Vernet Patrick, Britan Aurore, Gueux Elyette, Mazur Andrzej, Drevet Joël R
Laboratoire "Epididyme and Maturation des Gamètes", Université Blaise Pascal, CNRS UMR 6547, 24 avenue des Landais, 63177 Aubière cedex, France.
Biochim Biophys Acta. 2004 Nov 18;1675(1-3):32-45. doi: 10.1016/j.bbagen.2004.08.014.
It is well documented that a dietary deficiency in magnesium can induce oxidative stress and an inflammatory response in animal models. In our study, we have investigated these responses in the mouse epididymis after mice had been fed a magnesium-deficient diet for a 2-week duration. The extracellular and intracellular concentrations of magnesium where shown to be depleted on this diet. This was followed, however, only in the liver of the Mg-deficient animals, by an increase in both alpha 2-macroglobulin (alpha-2m), an acute phase marker, and interleukin-6 transcripts suggesting that an inflammatory response had been initiated. These changes were correlated with a decrease in circulating neutrophils. To address the question of whether or not peroxidation was induced in mouse epididymis following hypomagnesia, we have monitored the level of endogenous peroxidation, their ability to respond to induced peroxidation as well as the expression and activity of the enzymatic glutathione peroxidase (GPX) antioxidant family. To evaluate if the epididymis had evolved specific protections against peroxidation, other organs such as the liver and the kidney were monitored in parallel. We detected no evidence for increased peroxidation in any of the mouse organs tested. However, GPX activity was found to be significantly lower in the liver and the kidney of Mg-deficient animals while it was unchanged in the epididymides of the same animals during the deficiency. Histological analysis of the epididymis showed no major difference in the overall cytological aspect of the organ. Segment 2 of the caput, however presented a significant increase in the number of apically located cells or blebbing cells. Immunohistochemical analysis proved that these cells were epididymal apical cells and not infiltrated leukocytes. These observations suggested that the mouse caput epididymidis segment 2 specifically responded to Mg deficiency via the apical cells. Finally, a comparative analysis of stress response genes was conducted in control and magnesium-deficient caput epididymidis samples. It brought forward some genes that might be involved in the peculiar response of the caput epithelium following hypomagnesia.
有充分的文献记载，在动物模型中，膳食中镁缺乏会诱发氧化应激和炎症反应。在我们的研究中，我们对小鼠喂食缺镁饮食两周后附睾中的这些反应进行了研究。结果显示，这种饮食导致细胞外和细胞内的镁浓度降低。然而，仅在缺镁动物的肝脏中，急性期标志物α2-巨球蛋白（α-2m）和白细胞介素-6转录本均增加，这表明炎症反应已经启动。这些变化与循环中性粒细胞的减少相关。为了解低镁血症后小鼠附睾是否会诱导过氧化反应，我们监测了内源性过氧化水平、它们对诱导过氧化的反应能力以及酶促谷胱甘肽过氧化物酶（GPX）抗氧化家族的表达和活性。为了评估附睾是否进化出了针对过氧化的特异性保护机制，同时对肝脏和肾脏等其他器官进行了监测。我们在任何测试的小鼠器官中均未发现过氧化增加的证据。然而，发现缺镁动物肝脏和肾脏中的GPX活性显著降低，而在缺镁期间同一动物的附睾中该活性未发生变化。附睾的组织学分析显示，该器官的整体细胞学方面没有重大差异。然而，头部的第2节段顶端定位细胞或泡状细胞的数量显著增加。免疫组织化学分析证明这些细胞是附睾顶端细胞，而非浸润的白细胞。这些观察结果表明，小鼠附睾头部第2节段通过顶端细胞对镁缺乏有特异性反应。最后，对对照和缺镁附睾头部样本中的应激反应基因进行了比较分析。结果提出了一些可能参与低镁血症后附睾上皮特殊反应的基因。
