Zinc protects against apoptosis of endothelial cells induced by linoleic acid and tumor necrosis factor alpha.
Zinc protects against apoptosis of endothelial cells induced by linoleic acid and tumor necrosis factor alpha.
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DOI：
10.1093/ajcn/71.1.81
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发表时间：
2000
期刊：
影响因子：
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通讯作者：
P. Meerarani;P. Ramadass;M. Toborek;H. Bauer;H. Bauer;B. Hennig
中科院分区：
文献类型：
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作者：
P. Meerarani;P. Ramadass;M. Toborek;H. Bauer;H. Bauer;B. Hennig
背景血管内皮对锌的需求可能在炎症状态下增加，即动脉粥样硬化，其中凋亡细胞死亡是普遍的。目的我们推测锌缺乏可能通过增强导致细胞凋亡和caspase基因上调的途径，增强由脂肪酸和炎性细胞因子介导的内皮细胞完整性的破坏。设计内皮细胞在低血清培养基中培养或在含有选择的螯合剂，即二亚乙基三胺五乙酸盐或N，N，N '，N'-四（2-吡啶甲基）乙二胺（TPEN）的培养基中生长，有或没有锌补充。随后，用亚油酸、肿瘤坏死因子α（TNF-α）或两者处理细胞。我们研究了缺锌和补锌对细胞凋亡诱导的影响，通过测量caspase-3活性，细胞膜联蛋白V的结合，和DNA片段。结果亚油酸和TNF-α单独作用，但协同作用更显著，可上调caspase-3活性，诱导膜联蛋白V结合和DNA片段化。与对照培养物相比，缺锌，尤其是由TPEN诱导时，显着增加了细胞因子和脂质诱导的细胞凋亡死亡。补充低血清或螯合剂处理的内皮细胞与生理量的锌引起亚油酸和TNF-α诱导的细胞凋亡的显着衰减。缺锌时观察到的细胞形态学变化可通过补锌来预防。培养基中补充其他二价阳离子（如钙和镁）没有模拟锌对细胞凋亡的保护作用。结论：我们的数据表明，锌是至关重要的血管内皮细胞的完整性，可能是通过调节信号事件，以抑制细胞凋亡。
BACKGROUND Zinc requirements of the vascular endothelium may be increased in inflammatory conditions, ie, atherosclerosis, in which apoptotic cell death is prevalent. OBJECTIVE We hypothesized that zinc deficiency may potentiate disruption of endothelial cell integrity mediated by fatty acids and inflammatory cytokines by enhancing pathways that lead to apoptosis and up-regulation of caspase genes. DESIGN Endothelial cells were maintained in low-serum medium or grown in culture media containing selected chelators, ie, diethylenetriaminepentaacetate or N,N,N', N'-tetrakis(2-pyridylmethyl)-ethylenediamine (TPEN), with or without zinc supplementation. Subsequently, cells were treated with linoleic acid, tumor necrosis factor alpha (TNF-alpha), or both. We studied the effect of zinc deficiency and supplementation on the induction of apoptosis by measuring caspase-3 activity, cell binding of annexin V, and DNA fragmentation. RESULTS Our results indicated that linoleic acid and TNF-alpha independently, but more markedly in concert, up-regulated caspase-3 activity and induced annexin V binding and DNA fragmentation. Zinc deficiency, especially when induced by TPEN, dramatically increased apoptotic cell death induced by cytokines and lipids compared with control cultures. Supplementation of low-serum- or chelator-treated endothelial cells with physiologic amounts of zinc caused a marked attenuation of apoptosis induced by linoleic acid and TNF-alpha. Morphologic changes of cells observed during zinc deficiency were prevented by zinc supplementation. Media supplementation with other divalent cations (eg, calcium and magnesium) did not mimic the protective role of zinc against apoptosis. CONCLUSIONS Our data indicate that zinc is vital to vascular endothelial cell integrity, possibly by regulating signaling events to inhibit apoptotic cell death.