Effect of Poria cocos on hypertonic stress-induced water channel expression and apoptosis in renal collecting duct cells

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• 作者：So Min Lee^a ; ^b ; Yun Jung Lee^a ; ^b ; Jung Joo Yoon^a ; ^b ; Dae Gill Kang^a ; ^b ; ^{dgkang@wku.ac.kr} ; Ho Sub Lee^a ; ^b ; ^{host@wku.ac.kr}
• 关键词：Hypertonicity ; AQP2 ; Renal medullar collecting duct ; Apoptosis ; PKA
• 刊名：Journal of Ethnopharmacology
• 出版年：2012
• 期刊代码：26_03788741
• 类别：pha
• 出版时间：7 May, 2012
• 卷：141
• 期：1
• 页码：368-376
• 文件大小：1474 K

摘要

Ethnopharmacological relevance

A major physiological role of the kidney is to regulate body water and urine concentration. Aquaporin-2 (AQP2), a family of water channels, plays an important role in the urinary concentrating process and regulation of water balance in the kidney. The dried sclerotia of Poria cocos Wolf has been known to have a diuretic effect and used for the treatment of chronic edema and nephrosis.

Aim of the study

This study was conducted to evaluate the inhibitory effect of the sclerotia of Poria cocos (WPC) on hypertonic stress-induced AQP2 expression and apoptosis in inner medullary collecting duct cell lines (IMCD-3).

Materials and methods

Hypertonic stress was induced by 175 mM NaCl. Inhibitory effect of WPC on hypertonic stress-induced AQP2 expression and apoptosis were determined by western blot, RT-PCR, and immunofluorescence.

Results

Hypertonic stress (175 mM NaCl) increased in the levels of AQP2 expression by hypertonicity in IMCD-3 cells. WPC attenuated the hypertonicity-induced increase in protein and mRNA levels of AQP2 in a concentration-dependent manner. Pretreatment with WPC attenuated hypertonicity-induced cell death. Hypertonicity increased serum- and glucocorticoid-inducible protein kinase (Sgk1) phosphorylation, however, WPC attenuated the hypertonicity-induced Sgk1 activation. Tonicity-responsive enhancer binding protein (TonEBP) mRNA was also recovered by WPC under hypertonic stress. Pretreatment with WPC presented the similar effect of PKA inhibitor which decreased hypertonic stress-induced AQP2 expression. Hypertonicity increased cAMP levels and the changes were blocked by WPC. On the other hand, hypertonic stress-induced Bax or caspase-3 expression was decreased by WPC, resulting in anti-apoptotic effect.

Conclusions

These results provided evidence that the beneficial effect of WPC in water balance against in vitro hypertonic stress of renal collecting ducts. In addition, WPC exhibits anti-apoptotic property response to hypertonic stress. Thus, these data suggests that WPC has benefit for the therapeutic approach to the inhibition of renal disorder.