Zinc protects against apoptosis of endothelial cells induced by linoleic acid and tumor necrosis factor α

P. Meerarani, P. Ramadass, Michal J Toborek, Hans Christian Bauer, Hannelore Bauer, Bernhard Hennig

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)81-87
Number of pages7
JournalAmerican Journal of Clinical Nutrition
Volume71
Issue number1
StatePublished - Jan 1 2000
Externally publishedYes

Fingerprint

tumor necrosis factors
Linoleic Acid
endothelial cells
Zinc
linoleic acid
apoptosis
Endothelial Cells
Tumor Necrosis Factor-alpha
zinc
Apoptosis
cell death
ethylenediamine
Cell Death
Annexin A5
DNA fragmentation
DNA Fragmentation
caspase-3
Chelating Agents
chelating agents
blood vessels

Keywords

  • Annexin V
  • Apoptosis
  • Apoptotic cell death
  • Atherosclerosis
  • Caspase-3
  • Cell destabilizing agents
  • Cytokines
  • Endothelial cells
  • Inflammatory conditions
  • Linoleic acid
  • Polyunsaturated lipids
  • Tumor necrosis factor α
  • Vascular endothelium
  • Zinc
  • Zinc deficiency
  • Zinc supplementation

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science

Cite this

Zinc protects against apoptosis of endothelial cells induced by linoleic acid and tumor necrosis factor α. / Meerarani, P.; Ramadass, P.; Toborek, Michal J; Bauer, Hans Christian; Bauer, Hannelore; Hennig, Bernhard.

In: American Journal of Clinical Nutrition, Vol. 71, No. 1, 01.01.2000, p. 81-87.

Research output: Contribution to journalArticle

Meerarani, P. ; Ramadass, P. ; Toborek, Michal J ; Bauer, Hans Christian ; Bauer, Hannelore ; Hennig, Bernhard. / Zinc protects against apoptosis of endothelial cells induced by linoleic acid and tumor necrosis factor α. In: American Journal of Clinical Nutrition. 2000 ; Vol. 71, No. 1. pp. 81-87.
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abstract = "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.",
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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 J

AU - Bauer, Hans Christian

AU - Bauer, Hannelore

AU - Hennig, Bernhard

PY - 2000/1/1

Y1 - 2000/1/1

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.

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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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