TY - JOUR
T1 - Zinc protects against apoptosis of endothelial cells induced by linoleic acid and tumor necrosis factor α
AU - Meerarani, P.
AU - Ramadass, P.
AU - Toborek, Michal
AU - Bauer, Hans Christian
AU - Bauer, Hannelore
AU - Hennig, Bernhard
PY - 2000/1
Y1 - 2000/1
N2 - 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, diethylene-triaminepentaacetate 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 α (TNF-α), 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-α 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-α. 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.
AB - 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, diethylene-triaminepentaacetate 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 α (TNF-α), 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-α 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-α. 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.
KW - Annexin V
KW - Apoptosis
KW - Apoptotic cell death
KW - Atherosclerosis
KW - Caspase-3
KW - Cell destabilizing agents
KW - Cytokines
KW - Endothelial cells
KW - Inflammatory conditions
KW - Linoleic acid
KW - Polyunsaturated lipids
KW - Tumor necrosis factor α
KW - Vascular endothelium
KW - Zinc
KW - Zinc deficiency
KW - Zinc supplementation
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U2 - 10.1093/ajcn/71.1.81
DO - 10.1093/ajcn/71.1.81
M3 - Article
C2 - 10617950
AN - SCOPUS:0033967061
SN - 0002-9165
VL - 71
SP - 81
EP - 87
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
IS - 1
ER -