The protective effect of alpha-tocopherol against dichromate-induced renal tight junction damage is mediated via ERK1/2
The protective effect of alpha-tocopherol against dichromate-induced renal tight junction damage is mediated via ERK1/2
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DOI：
10.1016/j.toxlet.2009.09.011
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发表时间：
2009-12-15
影响因子：
3.5
通讯作者：
Reyes, Jose L.
中科院分区：
文献类型：
--
作者：
Arreola-Mendoza, Laura;Del Razo, Luz M.;Reyes, Jose L.
肾紧密连接（TJ）在调节细胞旁信号通路中起着重要作用。我们检测了急性肾功能衰竭（ARF）伴氧化损伤模型中TJ蛋白occludin和claudin-2（cln-2）在近曲小管上的功能、数量和分布。因为ERK 1/2-p调节TJ的完整性。我们研究了它们在重铬酸盐（Cr 6-）毒性中的参与。我们评估是否共同管理的抗氧化剂α-生育酚（α-TOC）防止Cr 6+毒性TJ雌性Wistar大鼠重铬酸钾15毫克/公斤，SC（5 - 3毫克/公斤的Cr 6+）单剂量。有或没有α-TOC（125 mg/kg. po.每日）。Cr 6+处理后2天和7天，通过肾脏脂质过氧化（LPO）评估氧化损伤，通过钠和葡萄糖排泄分数评估近端功能。免疫荧光法和Western blot法检测Occludin、cln-2和ERK 1/2-p的表达。Cr 6+诱导的ARF引起尿钠和葡萄糖丢失增加，occludin数量增加（第2天和第7天分别为6.6和15倍）和cln-2的错误定位。电泳迁移仅在Cr 6+给药组中显示出较高分子量条带，表明occludin过度磷酸化α-TOC处理减少了LPO。改善肾小管功能。并保留TJ的位置和表达。综上所述，我们发现在Cr 6+中毒诱导的ARF中occludin和cln-2被破坏。这项研究提供了证据，证明α-TOC对受到氧化损伤的TJ结构和功能具有有益作用，我们建议ERK 1/2参与抗氧化剂的保护机制（C）2009 Elsevier爱尔兰Ltd.保留所有权利
Renal tight junctions (TJ) play a central role in modulating the paracellular pathway We examined the function, quantity and distribution of TJ proteins occludin and claudin-2 (cln-2), on proximal tubule in a model of acute renal failure (ARF) associated with oxidative damage. Since ERK1/2-p modulates TJ integrity. we studied their participation in dichromate (Cr6-) toxicity. We evaluated whether co-administration of the antioxidant alpha-tocopherol (alpha-TOC) prevents Cr6+ toxicity in TJ Female Wistar rats received potassium dichromate 15 mg/kg, sc (5 3 mg/kg of Cr6+) single dose. with or without alpha-TOC (125 mg/kg. po. daily). Two and 7 days after Cr6+ treatment, oxidative damage was assessed by renal lipid peroxidation (LPO), proximal function was estimated by sodium and glucose fractional excretions. Occludin, cln-2, and ERK1/2-p were detected by immunofluorescence and Western blot. ARF induced by Cr6+ provoked augment in the sodium and glucose urinary looses, increases in occludin quantity (6.6- and 15-fold on days 2 and 7, respectively) and the mislocation of cln-2. Electrophoresis migration showed a higher molecular weight band only in the Cr6+-administered groups, suggesting occludin hyperphosphorylation alpha-TOC treatment diminished the LPO. improved tubular function. and preserved TJ location and expression. In summary, we show disruption of occludin and cln-2 in ARF induced by Cr6+-intoxication This study provides evidence of the beneficial effect of alpha-TOC on TJ structure and function undergoing oxidative damage, and we suggest the participation of ERK1/2 in the mechanisms leading to protection by the antioxidant (C) 2009 Elsevier Ireland Ltd. All rights reserved