主页 > 医学新闻 >
【文摘发布】线粒体是白蛋白致近曲小管上皮细
J Am Soc Nephrol 18: 1199-1208, 2007
Elif Erkan*,, Prasad Devarajan and George J. Schwartz*
Nephrotic-range proteinuria is considered a poor prognostic factor. A correlation between tubulointerstitial injury and the degree of proteinuria is well established. In an attempt to explain the tubular atrophy that is observed in advanced glomerulonephritides, this study investigated apoptotic mechanisms in cultured human proximal tubule cells (HKC-8) that were exposed to endotoxin-free albumin (5, 10, and 20 mg/ml). Apoptosis was detected by Hoechst 33342; annexin staining; and assays for caspases 3, 8, and 9. The apoptotic effect of albumin was maximal at 10 mg/ml albumin, and necrosis prevailed in cells that were incubated with 20 mg/ml. Increase in caspase-9 and -3 activity was observed starting at 6 and maximally at 16 to 24 h. The proapoptotic Bcl-2 protein Bax was upregulated at 6 h, associated with translocation of cytochrome-c from mitochondria to cytosol and alteration in the mitochondrial membrane potential. Production of reactive oxygen species (ROS) was significant at 6 h but declined at 16 and 24 h. Treatment with ROS scavenger dimethylthiourea or antioxidant N-acetylcysteine did not alleviate caspase-3 production. Pan protein kinase C inhibitor bisindolylmaleimide-1 protected the cells from apoptosis. It is concluded that albumin induces apoptosis in human proximal tubule cells by stimulating mitochondrial apoptotic pathway independent of ROS production. 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 题目: 线粒体是白蛋白致近曲小管上皮细胞凋亡的靶器官
作者: Elif Erkan*,, Prasad Devarajan and George J. Schwartz
来源: J Am Soc Nephrol 18: 1199-1208, 2007
肾病范围的蛋白尿被认为是一种预后较差的因素.小管间质损伤和蛋白尿程度之间有关联这一结论比较公认的.为了解释在严重肾小球肾炎中小管的萎缩,这篇文章主要研究肾小管细胞的凋亡机制,将人近端肾小管细胞 (HKC-8)与无内毒素白蛋白(浓度分别为5, 10, and 20 毫克/毫升)共同培养.凋亡用Hoechst 33342; annexin staining和caspases 3, 8, and 9来检测.白蛋白引起凋亡最大剂量为10毫克/毫升,当白蛋白为20毫克/毫升则主要引起坏死.在6个小时和最长16到20个小时,caspase-9 and -3活性增加.促凋亡Bcl-2蛋白Bax 在6个小时上调,这与细胞色素C从线立体易位到胞质和线立体膜电压改变有关.氧化应激产物(ROS) 主要在共培养6个小时内产生,在16到24小时则呈下降趋势.用氧化应激产物抑制剂二甲叉三脲或抗氧化剂N-乙酰半胱氨酸干预并没有使 caspase-3减弱.pan蛋白激酶C抑制 bisindolylmaleimide-1剂可以保护细胞免受凋亡.因此白蛋白诱导人近端小管凋亡主要是通过激活线立体途径,不依赖于氧化应激产物. 请squall老师指教! [标签:content1][标签:content2]
阅读本文的人还阅读：
作者:admin@医学,生命科学 2011-07-04 18:02
医学,生命科学网