PMID- 10381560
OWN - NLM
STAT- MEDLINE
DCOM- 19990811
LR  - 20190610
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1454
IP  - 2
DP  - 1999 Jul 7
TI  - Kinetics of hemin distribution in plasma reveals its role in lipoprotein
      oxidation.
PG  - 153-64
AB  - Hemin is a powerful in vitro inducer of low-density lipoprotein (LDL) oxidation, 
      implicated in development of atherosclerosis. To support the proposed role of
      hemin in atherogenesis, the question of whether hemin has any chance of getting
      together with LDL in vivo, must be addressed. A stopped-flow technique was
      employed in order to investigate the fast kinetics of hemin binding to LDL and to
      other plasma hemin-binding proteins: high-density lipoprotein (HDL), albumin and 
      hemopexin. Based on the measured rate constants of hemin association with and
      dissociation from each of these proteins, time-dependent hemin distribution in
      plasma was analyzed. The analysis shows that as much as 80% of total hemin binds 
      initially to LDL and HDL, the plasma components which are most susceptible to
      oxidation. Only then hemin partially transfers to the antioxidants albumin and
      hemopexin. The half time of the hemin-LDL complex in plasma, initially comprising
      27% of total hemin, was more than 20 s. Not only transient, but also oxidatively 
      active steady-state hemin-lipoprotein complexes in plasma were both predicted
      from the kinetic analysis and found in experiment. Our data suggest that the
      hemin-LDL complex may exist in vivo and that its oxidative potential should be
      considered pro-atherogenic.
FAU - Miller, Y I
AU  - Miller YI
AD  - Sackler Institute of Molecular Medicine, Department of Human Genetics and
      Molecular Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv
      69978, Israel. yumiller@ucsd.edu
FAU - Shaklai, N
AU  - Shaklai N
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Lipoproteins, HDL)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Serum Albumin)
RN  - 743LRP9S7N (Hemin)
SB  - IM
MH  - Hemin/*chemistry
MH  - Humans
MH  - Kinetics
MH  - Lipoproteins, HDL/chemistry
MH  - Lipoproteins, LDL/blood/*chemistry
MH  - Oxidation-Reduction
MH  - Oxidative Stress
MH  - Serum Albumin/chemistry
EDAT- 1999/06/25 00:00
MHDA- 1999/06/25 00:01
CRDT- 1999/06/25 00:00
PHST- 1999/06/25 00:00 [pubmed]
PHST- 1999/06/25 00:01 [medline]
PHST- 1999/06/25 00:00 [entrez]
AID - S0925-4439(99)00027-7 [pii]
AID - 10.1016/s0925-4439(99)00027-7 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 1999 Jul 7;1454(2):153-64. doi:
      10.1016/s0925-4439(99)00027-7.