Differences in immunolocalization of Kim-1, RPA-1, and RPA-2 in kidneys of gentamicin-, cisplatin-, and valproic acid-treated rats: potential role of iNOS and nitrotyrosine.
Differences in immunolocalization of Kim-1, RPA-1, and RPA-2 in kidneys of gentamicin-, cisplatin-, and valproic acid-treated rats: potential role of iNOS and nitrotyrosine.
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DOI：
10.1177/0192623309339605
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发表时间：
2009-08
影响因子：
1.5
通讯作者：
Hanig JP
中科院分区：
文献类型：
--
作者：
Zhang J;Goering PL;Espandiari P;Shaw M;Bonventre JV;Vaidya VS;Brown RP;Keenan J;Kilty CG;Sadrieh N;Hanig JP
本研究比较了硫酸庆大霉素(GEN)和顺铂(Cisplatin)处理的大鼠肾脏中KIM-1、肾乳头状抗原(RPA)-1和RPA-2与诱导型一氧化氮合酶(INOS)和硝基酪氨酸的免疫定位。用丙戊酸(VPA)给大鼠灌胃，评价急性肾损伤(AKI)标志物、诱导型一氧化氮合酶(INOS)和硝基酪氨酸的特异性。SD大鼠皮下注射Gen 100 mg/kg/d，连续6天或14天；单次腹腔注射顺铂1、3、6 mg/kg，或VPA 650 mg/kg/d，连续4天。Gen处理组大鼠大脑皮质集合管(CD)上皮细胞表达KIM-1，主要表达于S1/S2段，S3段表达较少，RPA-1表达增强。检测iNOS和硝基酪氨酸与Kim-1或RPA-1的空间表达。顺铂组大鼠仅在S3节段细胞表达Kim-1，RPA-1和RPA-2分别在延髓CD和Henle延髓环上皮细胞表达。诱导型一氧化氮合酶或硝基酪氨酸与RPA-1或RPA-2的空间表达也被证实。这些发现提示过氧亚硝酸盐的形成可能参与GEN和Cis肾毒性的发病机制，Kim-1、RPA-1和RPA-2有可能作为Gen或Cis AKI的部位特异性生物标志物。
The present study compared the immunolocalization of Kim-1, renal papillary antigen (RPA)-1, and RPA-2 with that of inducible nitric oxide synthase (iNOS) and nitrotyrosine in kidneys of gentamicin sulfate (Gen)- and cisplatin (Cis)-treated rats. The specificity of acute kidney injury (AKI) biomarkers, iNOS, and nitrotyrosine was evaluated by dosing rats with valproic acid (VPA). Sprague-Dawley (SD) rats were injected subcutaneously (sc) with 100 mg/kg/day of Gen for six or fourteen days; a single intraperitoneal (ip) dose of 1, 3, or 6 mg/kg of Cis; or 650 mg/kg/day of VPA (ip) for four days. In Gen-treated rats, Kim-1 was expressed in the epithelial cells, mainly in the S1/S2 segments but less so in the S3 segment, and RPA-1 was increased in the epithelial cells of collecting ducts (CD) in the cortex. Spatial expression of iNOS or nitrotyrosine with Kim-1 or RPA-1 was detected. In Cis-treated rats, Kim-1 was expressed only in the S3 segment cells, and RPA-1 and RPA-2 were increased in the epithelial cells of medullary CD or medullary loop of Henle (LH), respectively. Spatial expression of iNOS or nitrotyrosine with RPA-1 or RPA-2 was also identified. These findings suggest that peroxynitrite formation may be involved in the pathogenesis of Gen and Cis nephrotoxicity and that Kim-1, RPA-1, and RPA-2 have the potential to serve as site-specific biomarkers for Gen or Cis AKI.
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影响因子：
3.5
作者：
Lee, CC;Lee, YY;Lin, MT
通讯作者：
Lin, MT
影响因子：
1.5
作者：
Cristofori, Patrizia;Zanetti, Edoardo;Trevisan, Andrea
通讯作者：
Trevisan, Andrea
影响因子：
19.6
作者：
Chatterjee, PK;Cuzzocrea, S;Thiemermann, C
通讯作者：
Thiemermann, C
影响因子：
6.1
作者：
Hildebrand, H;Rinke, M;Falkenberg, FW
通讯作者：
Falkenberg, FW
影响因子：
2.2
作者：
Mark, LA;Robinson, AV;Schulak, JA
通讯作者：
Schulak, JA