Premium
Inactivation of Iron Responsive Element–binding Capacity and Aconitase Function of Iron Regulatory Protein‐1 of Skin Cells by Ultraviolet A
Author(s) -
Giordani Anne,
Martin MarieElise,
Beaumont Carole,
Santus René,
Morlière Patrice
Publication year - 2000
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1562/0031-8655(2000)0720746ioireb2.0.co2
Subject(s) - chemistry , oxidative stress , singlet oxygen , aconitase , reactive oxygen species , catalase , biochemistry , superoxide , biophysics , superoxide dismutase , endogeny , oxygen , enzyme , biology , organic chemistry
The ultraviolet‐A (UVA) component of sunlight produces in cutaneous cells a highly toxic oxidative stress mediated by redox cycling reactions of Fe ions. A tight regulation of cell iron uptake and storage by iron regulatory proteins (IRP) of keratinocytes and fibroblasts avoids these damaging reactions. We report here that about 40 J/cm 2 of UVA are required to inactivate half of the binding capacity of apo‐IRP‐1 to iron responsive elements (IRE) of RNA whereas 15 J/cm 2 already inhibit half of the holo‐IRP‐1 aconitase activity. No increase in the holo‐IRP‐1 activity is observed during the apo‐IRP‐1 photoinactivation suggesting that UVA does not trigger a shift between these two forms. As opposed to holo‐IRP‐1, which contains a 4Fe–4S cluster, apo‐IRP‐1 has no UVA chromophore. Thus it should be inactivated indirectly by reactive oxygen species generated by the UVA‐induced endogenous photo‐oxidative stress. The apo‐IRP‐1 photoinactivation is weakly prevented by the lipophilic oxyradical scavenger vitamin E but not by the hydrophilic azide anion, a singlet oxygen quencher or by diethyldithiocarbamate, a superoxide dismutase inhibitor. However, full protection against photoinactivation of the apo form is observed after incubation with N ‐acetylcysteine but the latter only partially protects the aconitase function of the holo‐IRP‐1 from photoinactivation. The marked difference in the kinetics of photoinactivation of the apo and holo forms, the light dose–independent effect of the sulfhydril group reagent, 2‐mercaptoethanol and the partial protection brought by the ferric ion complexing agent desferrioxamine suggest that the photochemistry of the 4Fe–4S cluster of the holo form plays little, if any, role in the photoinactivation of the apo‐IRP‐1/IRE interaction. It is concluded that the apo/holo equilibrium is irreversibly destroyed by UVA irradiation.