Calcium oxalate toxicity in renal epithelial cells: the mediation of crystal size on cell death mode.
Calcium oxalate toxicity in renal epithelial cells: the mediation of crystal size on cell death mode.
复制标题
草酸钙对肾上皮细胞的毒性：晶体大小对细胞死亡模式的介导。
DOI：
10.1038/cddiscovery.2015.55
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发表时间：
2015
影响因子：
7
通讯作者：
Ouyang JM
中科院分区：
文献类型：
--
作者：
Sun XY;Gan QZ;Ouyang JM
草酸钙（CaOx）对肾上皮细胞的细胞毒性已被广泛研究，但不同物理性质（如晶体大小和晶相）的CaOx诱导的细胞死亡模式尚未得到详细研究。本研究比较了纳米级（50 nm）和微米级（10 μm）一水草酸钙（COM）和二水草酸钙（COD）诱导细胞死亡方式的差异，以探讨细胞死亡机制。通过检测细胞骨架变化、溶酶体完整性、线粒体膜电位（Δ Tcm）、凋亡和/或坏死、骨桥蛋白（OPN）表达和丙二醛（MDA）释放，研究纳米/微米级COM和COD晶体暴露对非洲绿色猴肾上皮（Vero）细胞的影响。纳米/微米COM和COD晶体可同时引起细胞凋亡和坏死。纳米尺寸的晶体主要引起凋亡性细胞死亡，导致细胞收缩、磷脂酰丝氨酸外翻和核收缩，而微米尺寸的晶体主要引起坏死性细胞死亡，导致细胞肿胀和细胞膜和溶酶体破裂。纳米尺寸的COM和COD晶体比微米尺寸的晶体诱导更大的细胞死亡（凋亡和坏死的总和），COM晶体比相同尺寸的COD晶体显示出更高的细胞毒性。凋亡和坏死均可导致线粒体去极化，OPN表达增加，脂质过氧化产物MDA生成增加。OPN表达量和MDA生成量与细胞损伤程度呈正相关。晶体的理化性质可以影响细胞的死亡方式。本研究结果可为进一步研究细胞死亡机制提供依据。
The cytotoxicity of calcium oxalate (CaOx) in renal epithelial cells has been studied extensively, but the cell death mode induced by CaOx with different physical properties, such as crystal size and crystal phase, has not been studied in detail. In this study, we comparatively investigated the differences of cell death mode induced by nano-sized (50 nm) and micron-sized (10 μm) calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) to explore the cell death mechanism. The effect of the exposure of nano-/micron-sized COM and COD crystals toward the African green monkey renal epithelial (Vero) cells were investigated by detecting cell cytoskeleton changes, lysosomal integrity, mitochondrial membrane potential (Δψm), apoptosis and/or necrosis, osteopontin (OPN) expression, and malondialdehyde (MDA) release. Nano-/micron-sized COM and COD crystals could cause apoptosis and necrosis simultaneously. Nano-sized crystals primarily caused apoptotic cell death, leading to cell shrinkage, phosphatidylserine ectropion, and nuclear shrinkage, whereas micron-sized crystals primarily caused necrotic cell death, leading to cell swelling and cell membrane and lysosome rupture. Nano-sized COM and COD crystals induced much greater cell death (sum of apoptosis and necrosis) than micron-sized crystals, and COM crystals showed higher cytotoxicity than the same-sized COD crystals. Both apoptosis and necrosis could lead to mitochondria depolarization and elevate the expression of OPN and the generation of lipid peroxidation product MDA. The amount of expressed OPN and generated MDA was positively related to cell injury degree. The physicochemical properties of crystals could affect the cell death mode. The results of this study may provide a basis for future studies on cell death mechanisms.