Abstract
5-Aminolevulinic acid (ALA), a heme precursor accumulated in acute intermittent porphyria (AIP) and lead poisoning, undergoes metal-catalyzed oxidation in air-equilibrated solutions buffered at neutral pH, yielding free radicals (O2-, HO. and ALA.). The capacity of ALA to release iron from horse spleen and rat liver ferritin in vitro and to concomitantly initiate liposome lipid peroxidation was characterized. ALA induced iron release from ferritin in normally aerated solutions, in a dose (0.05-1 mM)- and time (0-120 min)-dependent manner; no reaction occurs under nitrogen. Superoxide dismutase partially inhibited (50% at 100 U/ml) iron release by 0.5 mM ALA, whereas the addition of catalase (50 U/ml) had no effect under these conditions. In phosphatidylcholine: cardiolipin (80:20) liposomes, and in the presence of 2 μmM EDTA, ALA (0.025-1 mM) per se had a subtle effect on lipid peroxidation, while after addition of ferritin (0.25 mg/ml) there was a significant increase in lipid peroxidation as evaluated by dose-dependent formation of 2-thiobarbituric-reactive substances and diene conjugation. In vivo, iron accumulation in the liver of ALA-treated rats was observed. Altogether, these data demonstrate the ability of ALA-generated free radicals to release iron from ferritin and to affect iron metabolism in vivo. ALA-mediated iron release from ferritin, therefore, may aggravate oxidative damage to cell components and contribute to the pathology observed in AIP (eg., primary liver cancer) and lead poisoning.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 607-611 |
| Number of pages | 5 |
| Journal | Archives of Biochemistry and Biophysics |
| Volume | 316 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1995 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
- Biophysics
- Biochemistry
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5-Aminolevulinic Acid Induces Iron Release from Ferritin. / Oteiza, P. I.; Kleinman, C. G.; Demasi, M.; Bechara, E. J H.
In: Archives of Biochemistry and Biophysics, Vol. 316, No. 1, 01.1995, p. 607-611.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 5-Aminolevulinic Acid Induces Iron Release from Ferritin
AU - Oteiza, P. I.
AU - Kleinman, C. G.
AU - Demasi, M.
AU - Bechara, E. J H
PY - 1995/1
Y1 - 1995/1
N2 - 5-Aminolevulinic acid (ALA), a heme precursor accumulated in acute intermittent porphyria (AIP) and lead poisoning, undergoes metal-catalyzed oxidation in air-equilibrated solutions buffered at neutral pH, yielding free radicals (O2-, HO. and ALA.). The capacity of ALA to release iron from horse spleen and rat liver ferritin in vitro and to concomitantly initiate liposome lipid peroxidation was characterized. ALA induced iron release from ferritin in normally aerated solutions, in a dose (0.05-1 mM)- and time (0-120 min)-dependent manner; no reaction occurs under nitrogen. Superoxide dismutase partially inhibited (50% at 100 U/ml) iron release by 0.5 mM ALA, whereas the addition of catalase (50 U/ml) had no effect under these conditions. In phosphatidylcholine: cardiolipin (80:20) liposomes, and in the presence of 2 μmM EDTA, ALA (0.025-1 mM) per se had a subtle effect on lipid peroxidation, while after addition of ferritin (0.25 mg/ml) there was a significant increase in lipid peroxidation as evaluated by dose-dependent formation of 2-thiobarbituric-reactive substances and diene conjugation. In vivo, iron accumulation in the liver of ALA-treated rats was observed. Altogether, these data demonstrate the ability of ALA-generated free radicals to release iron from ferritin and to affect iron metabolism in vivo. ALA-mediated iron release from ferritin, therefore, may aggravate oxidative damage to cell components and contribute to the pathology observed in AIP (eg., primary liver cancer) and lead poisoning.
AB - 5-Aminolevulinic acid (ALA), a heme precursor accumulated in acute intermittent porphyria (AIP) and lead poisoning, undergoes metal-catalyzed oxidation in air-equilibrated solutions buffered at neutral pH, yielding free radicals (O2-, HO. and ALA.). The capacity of ALA to release iron from horse spleen and rat liver ferritin in vitro and to concomitantly initiate liposome lipid peroxidation was characterized. ALA induced iron release from ferritin in normally aerated solutions, in a dose (0.05-1 mM)- and time (0-120 min)-dependent manner; no reaction occurs under nitrogen. Superoxide dismutase partially inhibited (50% at 100 U/ml) iron release by 0.5 mM ALA, whereas the addition of catalase (50 U/ml) had no effect under these conditions. In phosphatidylcholine: cardiolipin (80:20) liposomes, and in the presence of 2 μmM EDTA, ALA (0.025-1 mM) per se had a subtle effect on lipid peroxidation, while after addition of ferritin (0.25 mg/ml) there was a significant increase in lipid peroxidation as evaluated by dose-dependent formation of 2-thiobarbituric-reactive substances and diene conjugation. In vivo, iron accumulation in the liver of ALA-treated rats was observed. Altogether, these data demonstrate the ability of ALA-generated free radicals to release iron from ferritin and to affect iron metabolism in vivo. ALA-mediated iron release from ferritin, therefore, may aggravate oxidative damage to cell components and contribute to the pathology observed in AIP (eg., primary liver cancer) and lead poisoning.
UR - http://www.scopus.com/inward/record.url?scp=0028861658&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028861658&partnerID=8YFLogxK
U2 - 10.1006/abbi.1995.1080
DO - 10.1006/abbi.1995.1080
M3 - Article
C2 - 7840672
AN - SCOPUS:0028861658
VL - 316
SP - 607
EP - 611
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
SN - 0003-9861
IS - 1
ER -