Mishandling of copper by albumin: role in redox-cycling and oxidative stress in preeclampsia plasma.
OBJECTIVE
To test the hypothesis that enhanced oxidative stress during pregnancies complicated by preeclampsia is associated with improper copper (Cu) binding by plasma albumin, resulting in enhanced Cu redox-cycling activity and that altered Cu binding, in turn, is caused by interactions of excessive amounts of free fatty acids with albumin.


METHODS
We studied binding and redox-cycling activity of Cu in 17 normal pregnancy and 17 preeclampsia plasma samples. Binding of exogenous Cu in plasma samples was quantified indirectly using spectrophotometric measurements of its complex with a specific chelator of Cu(I), bathocuproine disulfonate. Redox-cycling activity of Cu in plasma samples was estimated by electron paramagnetic resonance (EPR) spectroscopy of ascorbate radicals formed during one-electron oxidation of ascorbate by redox-active catalytic Cu. Formation of Cu/albumin complexes in model systems in the presence and absence of fatty acids was studied using EPR spectroscopy of Cu(II)/albumin.


RESULTS
We found that preeclampsia plasma (as compared to normal pregnancy plasma) (1) displays elevated endogenous ascorbate redox-cycling that is normalized by a Cu(II) chelator, cuprizone I, (2) has lowered capacity to bind and redox-regulate exogenously added Cu, and (3) responds to treatment with fatty-acid-free albumin by diminished ascorbate oxidizing activity. Conversely, addition of free fatty acid (oleic acid) to normal pregnancy plasma sample yields increased ascorbate redox-cycling activity. Our model experiments showed that Cu-dependent redox-cycling activity of purified human serum albumin is significantly increased by excess free fatty acids.


CONCLUSIONS
Mishandling of Cu by albumin contributes to oxidative stress in preeclampsia. Cu chelators may represent promising mechanism-based antioxidants to attenuate oxidative stress in preeclampsia.
Kagan
V E
VE
Department of Environmental and Occupational Health, and Magee Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15238, USA. Kagan@pitt.edu
Tyurin
V A
VA
Borisenko
G G
GG
Fabisiak
J P
JP
Hubel
C A
CA
Ness
R B
RB
Gandley
R
R
McLaughlin
M K
MK
Roberts
J M
JM
D000328:Adult; D003300:Copper / Q000378:metabolism*; D005260:Female; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D012709:Serum Albumin / Q000378:metabolism*
D012709:Serum Albumin; D003300:Copper