Curcumin activates the p38MPAK-HSP25 pathway in vitro but fails to attenuate diabetic nephropathy in DBA2J mice despite urinary clearance documented by HPLC.
Curcumin activates the p38MPAK-HSP25 pathway in vitro but fails to attenuate diabetic nephropathy in DBA2J mice despite urinary clearance documented by HPLC.
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DOI：
10.1186/1472-6882-10-67
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发表时间：
2010-11-12
影响因子：
--
通讯作者：
Adler SG
中科院分区：
文献类型：
--
作者：
Ma J;Phillips L;Wang Y;Dai T;LaPage J;Natarajan R;Adler SG
姜黄素具有抗炎、抗氧化和抗增殖特性，并且根据实验情况，可以是促凋亡或抗凋亡的。这些生物学作用中有许多可以改善糖尿病肾病。小鼠足细胞，培养在基础或高葡萄糖条件下，进行急性暴露于姜黄素。进行p38-MAPK、考克斯-2和裂解的半胱天冬酶-3的蛋白质印迹; HSP 25磷酸化的等电聚焦;和F-至G-肌动蛋白裂解的DNase I测定用于体外分析。体内研究检查了饮食姜黄素对DBA 2 J小鼠中链脲佐菌素（Stz）诱导的糖尿病中糖尿病肾病发展的影响。获得尿白蛋白与肌酐的比值，进行高效液相色谱法测定尿姜黄素，并进行蛋白质印迹法测定p38-MAPK和总HSP 25。姜黄素增强p38 MAPK和下游HSP 25的磷酸化;抑制考克斯-2;诱导F-至G-肌动蛋白裂解减弱的趋势;并在体外显著抑制caspase-3的活化。在用姜黄素治疗的患有Stz糖尿病的DBA 2 J小鼠中，HPLC测量证实了尿姜黄素的存在。然而，在诱导糖尿病之前或之后饮食提供姜黄素未能减轻蛋白尿。除了种属、品系、血糖控制的早期差异和/或给药效应外，未能调节白蛋白尿可能是由于喂食姜黄素的DBA 2 J小鼠肾HSP 25减少或12/15脂氧合酶途径刺激所致。此外，这些研究表明，定时尿液收集可能有助于监测姜黄素给药和肾脏药效学效应。
Curcumin has anti-inflammatory, anti-oxidant, and anti-proliferative properties, and depending upon the experimental circumstances, may be pro- or anti-apoptotic. Many of these biological actions could ameliorate diabetic nephropathy. Mouse podocytes, cultured in basal or high glucose conditions, underwent acute exposure to curcumin. Western blots for p38-MAPK, COX-2 and cleaved caspase-3; isoelectric focusing for HSP25 phosphorylation; and DNase I assays for F- to G- actin cleavage were performed for in vitro analyses. In vivo studies examined the effects of dietary curcumin on the development of diabetic nephropathy in streptozotocin (Stz)-induced diabetes in DBA2J mice. Urinary albumin to creatinine ratios were obtained, high performance liquid chromatography was performed for urinary curcuminoid measurements, and Western blots for p38-MAPK and total HSP25 were performed. Curcumin enhanced the phosphorylation of both p38MAPK and downstream HSP25; inhibited COX-2; induced a trend towards attenuation of F- to G-actin cleavage; and dramatically inhibited the activation of caspase-3 in vitro. In curcumin-treated DBA2J mice with Stz-diabetes, HPLC measurements confirmed the presence of urinary curcuminoid. Nevertheless, dietary provision of curcumin either before or after the induction of diabetes failed to attenuate albuminuria. Apart from species, strain, early differences in glycemic control, and/or dosing effects, the failure to modulate albuminuria may have been due to a decrement in renal HSP25 or stimulation of the 12/15 lipoxygenase pathway in DBA2J mice fed curcumin. In addition, these studies suggest that timed urine collections may be useful for monitoring curcumin dosing and renal pharmacodynamic effects.
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影响因子：
4.3
作者：
Babu, PS;Srinivasan, K
通讯作者：
Srinivasan, K
DOI：
10.1152/ajpgi.00141.2001
发表时间：
2002-05-01
影响因子：
4.5
作者：
Bitar, KN
通讯作者：
Bitar, KN
影响因子：
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作者：
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通讯作者：
Surh, YJ
影响因子：
5
作者：
Hartojo, Wibisono;Silvers, Amy L.;Chang, Andrew C.
通讯作者：
Chang, Andrew C.
影响因子：
19.6
作者：
Dunlop, ME;Muggli, EE
通讯作者：
Muggli, EE