Oxalate toxicity in renal epithelial cells: characteristics of apoptosis and necrosis.
Oxalate toxicity in renal epithelial cells: characteristics of apoptosis and necrosis.
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DOI：
10.1006/taap.1999.8835
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发表时间：
2000-01
影响因子：
3.8
通讯作者：
C. Miller;L. Kennington;R. Cooney;Y. Kohjimoto;L. C. Cao;T. Honeyman;J. Pullman;J. Jonassen;C. Scheid
中科院分区：
文献类型：
--
作者：
C. Miller;L. Kennington;R. Cooney;Y. Kohjimoto;L. C. Cao;T. Honeyman;J. Pullman;J. Jonassen;C. Scheid
对包括肾脏在内的各种组织的研究表明，毒素在某些条件下引起细胞凋亡，在其他条件下引起坏死。这种反应的性质对受伤组织有重要的影响，因为坏死细胞会引起炎症反应，而凋亡细胞则不会。因此，人们对确定由已知细胞毒素引起的细胞死亡模式非常感兴趣。目前的研究检查了肾上皮细胞对草酸盐的反应，草酸盐是肾脏排泄的代谢物，在病理生理浓度下产生氧化应激和肾细胞死亡。这些研究使用来自猪肾脏的肾上皮细胞系LLC-PK1细胞和来自正常大鼠肾脏的NRK- 52e （NRK）细胞，并比较草酸盐与已知凋亡药物的作用。评估了细胞和核形态、核大小、神经酰胺产生和DNA完整性的变化。抗凋亡基因产物bcl-2对草酸盐毒性的减弱能力也进行了评估。这些研究表明，草酸盐诱导的肾上皮细胞死亡表现出凋亡细胞死亡的几个特征，包括神经酰胺的产生增加，凋亡小体的丰度增加，以及对抗凋亡基因bcl-2表达水平的显著敏感性。草酸盐诱导的细胞死亡也表现出坏死细胞死亡的几个特征，在草酸盐处理后，大多数细胞表现出细胞和细胞核肿胀，TUNEL试验显示DNA断裂的证据很少。这些结果表明，有毒浓度的草酸盐可触发肾上皮细胞两种形式的细胞死亡。
Studies in various tissues, including the kidney, have demonstrated that toxins elicit apoptosis under certain conditions and necrosis under others. The nature of the response has important consequences for the injured tissue in that necrotic cells elicit inflammatory responses, whereas apoptotic cells do not. Thus, there has been considerable interest in defining the mode of cell death elicited by known cytotoxins. The present studies examined the response of renal epithelial cells to oxalate, a metabolite excreted by the kidney that produces oxidant stress and death of renal cells at pathophysiological concentrations. These studies employed LLC-PK1 cells, a renal epithelial cell line from pig kidney and NRK-52E (NRK) cells, a line from normal rat kidney, and compared the effects of oxalate with those of known apoptotic agents. Changes in cellular and nuclear morphology, in nuclear size, in ceramide production, and in DNA integrity were assessed. The ability of bcl-2, an anti-apoptotic gene product, to attenuate oxalate toxicity was also assessed. These studies indicated that oxalate-induced death of renal epithelial cells exhibits several features characteristic of apoptotic cell death, including increased production of ceramide, increased abundance of apoptotic bodies, and marked sensitivity to the level of expression of the anti-apoptotic gene bcl-2. Oxalate-induced cell death also exhibits several characteristics of necrotic cell death in that the majority of the cells exhibited cellular and nuclear swelling after oxalate treatment and showed little evidence of DNA cleavage by TUNEL assay. These results suggest that toxic concentrations of oxalate trigger both forms of cell death in renal epithelial cells.