Reductive release of iron from ferritin by cation free radicals of paraquat and other bipyridyls.

NADPH-cytochrome P-450 reductase-catalyzed reduction of paraquat promoted the release of iron from ferritin. Aerobically, iron release was inhibited approximately 60% by superoxide dismutase, whereas xanthine oxidase-dependent iron release was inhibited nearly 100%. This suggests that both superoxide and the paraquat cation radical can catalyze the release of iron from ferritin. Accordingly, under anaerobic conditions, the paraquat radical mediated a very rapid, complete release of iron from ferritin. Similarly, the cation free radicals of the closely related chemicals, diquat and benzyl viologen, also promoted iron release. ESR studies demonstrated that electron transfer from the paraquat cation radical to ferritin accounts for the reductive release of iron. The ferritin structure was not altered by exposure to the paraquat radical and also retained its ability to re-incorporate iron. These studies indicate that release of iron from ferritin may be a common feature contributing to free radical-mediated toxicities.

• Publication year

  1986

• Venue

  Journal of Biological Chemistry

• Publication date

  1986-10-05

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1016/s0021-9258(18)69271-3PMID 3020022
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• ESR evidence supports electron transfer from the paraquat cation radical to ferritin as the mechanism of reductive iron release, and ferritin remains structurally intact with retained capacity to re-incorporate iron.

  Confidence 0.90

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) reviewjaeyoung (rb9u4m834j) review
• Under anaerobic conditions, the paraquat radical drives a very rapid and complete release of iron from ferritin, and the cation radicals of diquat and benzyl viologen also promote iron release.

  Confidence 0.97

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) reviewjaeyoung (rb9u4m834j) review
• Aerobic iron release is only partly inhibited by superoxide dismutase, while xanthine oxidase-dependent iron release is almost completely inhibited, consistent with both superoxide and the paraquat cation radical catalyzing ferritin iron release.

  Confidence 0.95

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) reviewjaeyoung (rb9u4m834j) review
• NADPH-cytochrome P-450 reductase-catalyzed reduction of paraquat promotes release of iron from ferritin.

  Confidence 0.98

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) reviewjaeyoung (rb9u4m834j) review

• anaerobic conditions

  experimental condition

  Oxygen-free experimental conditions used to assess radical-mediated iron release.

  Aliases: anaerobiosis

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) reviewjaeyoung (rb9u4m834j) review
• benzyl viologen cation radical

  chemical radical

  The radical cation form of benzyl viologen tested alongside paraquat and diquat.

  Aliases: benzyl viologen radical

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) reviewjaeyoung (rb9u4m834j) review
• diquat cation radical

  chemical radical

  The radical cation form of diquat tested for its ability to promote iron release from ferritin.

  Aliases: diquat radical

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) reviewjaeyoung (rb9u4m834j) review
• electron transfer

  mechanism

  A redox process in which an electron moves from the paraquat radical to ferritin.

  Aliases: redox transfer

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) reviewjaeyoung (rb9u4m834j) review
• esr studies

  measurement method

  Electron spin resonance measurements used to probe radical interactions during ferritin iron release.

  Aliases: electron spin resonance studies, ESR

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) reviewjaeyoung (rb9u4m834j) review
• ferritin

  protein

  The iron-storage protein from which iron is released and later can re-incorporate iron.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) reviewjaeyoung (rb9u4m834j) review
• iron re-incorporation

  process

  Ferritin's retained ability to take up iron again after exposure to the radical conditions.

  Aliases: reincorporation of iron

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) reviewjaeyoung (rb9u4m834j) review
• iron release

  process

  The liberation of stored iron from ferritin into solution or a measurable free pool.

  Aliases: release of iron

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) reviewjaeyoung (rb9u4m834j) review
• nadph-cytochrome p-450 reductase

  enzyme

  An electron-transfer reductase that catalyzes reduction of paraquat in this system.

  Aliases: NADPH-cytochrome P450 reductase, NADPH-cytochrome P450 oxidoreductase

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) reviewjaeyoung (rb9u4m834j) review
• paraquat cation radical

  chemical radical

  The one-electron reduced radical form of paraquat examined as the reactive species in iron release.

  Aliases: paraquat radical, PQ+•

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) reviewjaeyoung (rb9u4m834j) review
• superoxide dismutase

  enzyme

  An enzyme used here to test whether superoxide contributes to ferritin iron release.

  Aliases: SOD

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) reviewjaeyoung (rb9u4m834j) review
• xanthine oxidase

  enzyme

  An oxidase system used to generate conditions associated with ferritin iron release in the experiments.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewAK (4715169a40) reviewjaeyoung (rb9u4m834j) review

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