Renal proximal tubules from old Fischer 344 rats grow into epithelial cells in cultures and exhibit increased oxidative stress and reduced D1 receptor function
Renal proximal tubules from old Fischer 344 rats grow into epithelial cells in cultures and exhibit increased oxidative stress and reduced D1 receptor function
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DOI：
10.1152/ajpcell.00367.2008
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发表时间：
2008-11-01
影响因子：
5.5
通讯作者：
Lokhandwala, Mustafa F.
中科院分区：
文献类型：
--
作者：
Asghar, Mohammad;Chillar, Annirudha;Lokhandwala, Mustafa F.
Asghar M，辣椒A，Lokhandwala Mf.来自老年Fischer 344大鼠的肾近端小管在培养中成长为上皮细胞，并表现出氧化应激增加和D1受体功能降低。Am J Physiol Cell Physiol 295：C1326-C1331,2008。2008年9月17日首次发表；DOI：10.1152/ajpcell.00367.2008。-早些时候，我们报道了老年Fischer 344(F344)和肥胖Zucker大鼠肾脏近端小管(RPT)的D1受体功能缺陷。然而，肥胖的Zucker大鼠RPT的受体功能缺陷不会遗传到这些动物的RPT的原代培养中。在这里，我们确定了老年F344大鼠RPT中的D1受体功能缺陷是否会遗传给原代培养。取老年(24个月)和成年(6个月)F344大鼠的RPT进行原代培养。显微镜研究表明，成年和老年大鼠培养的细胞是健康的，这是由细胞和细胞核的形状和大小决定的。D_1受体激动剂SKF-38393抑制成年大鼠细胞摄取~(86)Rb(Rb)，抑制Na-K-ATPase活性指数，但对老年大鼠有抑制作用。此外，SKF-38393还可增加成年大鼠细胞膜上[S-35]GTP-S结合受体的激活指数，但老年大鼠的增加幅度较小。此外，老年大鼠脑内D1R数量和受体蛋白水平均呈下降趋势。有趣的是，在老年大鼠的培养中，NADPH氧化酶GP(91Phox)亚单位和细胞蛋白羰基水平(氧化应激标记物)较高。这些结果表明，成年和老年F344大鼠的RPT在培养中可分化为上皮细胞。此外，老年大鼠培养的细胞处于较高的氧化应激水平，这可能是老年大鼠细胞中D1受体功能与成年大鼠相比降低的原因之一。
Asghar M, Chillar A, Lokhandwala MF. Renal proximal tubules from old Fischer 344 rats grow into epithelial cells in cultures and exhibit increased oxidative stress and reduced D1 receptor function. Am J Physiol Cell Physiol 295: C1326-C1331, 2008. First published September 17, 2008; doi: 10.1152/ajpcell.00367.2008.-Earlier we reported defects in D1 receptor function in renal proximal tubules (RPTs) of aged Fischer 344 (F344) and obese Zucker rats. However, the defects in the receptor function in RPTs of obese Zucker rats do not pass onto primary cultures of RPTs from these animals. Here, we determined whether the defects in D1 receptor function in RPTs of aged F344 rats pass onto the primary cultures. RPTs from aged (24-mo) and adult (6-mo) F344 rats were grown into primary cultures. The microscopic studies showed that cells in cultures from adult and old rats were healthy as determined by the shape and size of the cells and nuclei. D1 receptor agonist SKF-38393 produced inhibition of 86Rb (rubidium) uptake, index of Na-K-ATPase activity, in cells from adult rats, but this was reduced in old rats. Also, SKF-38393 increased the [S-35]GTP gamma S binding, index of receptor activation, in the membranes of cells from adult rats but to a lesser extent from old rats. Furthermore, there was a downward trend in the levels of D1 receptor numbers and in the receptor proteins in old rats. Interestingly, gp(91phox) subunit of NADPH oxidase and cellular protein carbonyl levels (oxidative stress marker) were higher in cultures from old rats. These results show that RPTs from adult and old F344 rats grow into epithelial cells in cultures. Furthermore, cells in cultures from old rats are at a higher level of oxidative stress, which may be contributing to the reduced D1 receptor function in the cells from old compared with adult rats.