Binding of iron and inhibition of iron-dependent oxidative cell injury by the 'calcium chelator' 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid (BAPTA)

Bradley E. Britigan, George T. Rasmussen, Charles D. Cox

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

A role for increases in intracellular calcium (Ca2+) has been suggested in the pathophysiology of various forms of oxidant mediated cell injury. In recent studies, we found that iron bound to the Pseudomonas aeruginosa siderophore, pyochelin, augments oxidant-mediated endothelial cell injury by catalyzing the formation of hydroxyl radical (HO.). To investigate the role of Ca2+ in this process, the effects of two Ca2+ chelating agents, Fura-2 and 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid (BAPTA), were assessed. BAPTA, but not Fura-2, was protective against H2O2/ferripyochelin-mediated injury. Subsequent data suggested that chelation of iron rather than Ca2+ by BAPTA was most likely responsible. Spectrophotometry demonstrated that both ferrous (Fe2+) and ferric (Fe3+) iron formed a complex with BAPTA. The affinity of BAPTA for the metals was Fe3+ > Ca2+ > Fe2+ BAPTA was found to decrease markedly iron catalyzed production of HO. and/or ferryl species when analyzed by spin trapping. Although our results do not definitively prove that BAPTA protects endothelial cells from ferripyochelin-associated damage by chelating iron, these data indicate chat caution must be exercised in utilizing protective effects of intracellular 'Ca2+ chelating agents' as evidence for a role of alterations in cellular Ca2+ levels in experimental conditions in which iron-mediated oxidant production is also occurring.

Original languageEnglish (US)
Pages (from-to)287-295
Number of pages9
JournalBiochemical Pharmacology
Volume55
Issue number3
DOIs
StatePublished - Feb 1 1998

Fingerprint

Iron
Cells
Wounds and Injuries
Oxidants
Endothelial cells
Chelating Agents
Chelation
Endothelial Cells
Spin Trapping
Siderophores
1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
Calcium Chelating Agents
Fura-2
Spectrophotometry
Hydroxyl Radical
Pseudomonas aeruginosa
Metals
Calcium

Keywords

  • BAPTA
  • Calcium
  • Endothelial cell
  • Ferryl species
  • Hydroxyl radical
  • Iron
  • Pyochelin
  • Spin trapping

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

Binding of iron and inhibition of iron-dependent oxidative cell injury by the 'calcium chelator' 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid (BAPTA). / Britigan, Bradley E.; Rasmussen, George T.; Cox, Charles D.

In: Biochemical Pharmacology, Vol. 55, No. 3, 01.02.1998, p. 287-295.

Research output: Contribution to journalArticle

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abstract = "A role for increases in intracellular calcium (Ca2+) has been suggested in the pathophysiology of various forms of oxidant mediated cell injury. In recent studies, we found that iron bound to the Pseudomonas aeruginosa siderophore, pyochelin, augments oxidant-mediated endothelial cell injury by catalyzing the formation of hydroxyl radical (HO.). To investigate the role of Ca2+ in this process, the effects of two Ca2+ chelating agents, Fura-2 and 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid (BAPTA), were assessed. BAPTA, but not Fura-2, was protective against H2O2/ferripyochelin-mediated injury. Subsequent data suggested that chelation of iron rather than Ca2+ by BAPTA was most likely responsible. Spectrophotometry demonstrated that both ferrous (Fe2+) and ferric (Fe3+) iron formed a complex with BAPTA. The affinity of BAPTA for the metals was Fe3+ > Ca2+ > Fe2+ BAPTA was found to decrease markedly iron catalyzed production of HO. and/or ferryl species when analyzed by spin trapping. Although our results do not definitively prove that BAPTA protects endothelial cells from ferripyochelin-associated damage by chelating iron, these data indicate chat caution must be exercised in utilizing protective effects of intracellular 'Ca2+ chelating agents' as evidence for a role of alterations in cellular Ca2+ levels in experimental conditions in which iron-mediated oxidant production is also occurring.",
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