Low-density lipoprotein oxidized to various degrees activates ERK1/2 through Lox-1.
Although the standard procedure for preparing extensively oxidized low-density lipoprotein (Ox-LDL) is to incubate it with 10muM CuSO(4) at 37 degrees C for 24h, it is not well known how important the degree of oxidation of LDL is for inducing cell signaling. Since Lox-1 (an Ox-LDL receptor) contributes to cell proliferation through extracellular-signal-regulated kinase (ERK)1/2 activation and subsequently induces plaque growth, we analyzed ERK activity using LDL with various degrees of oxidation, from minimally Ox-LDL, which is mainly in human plasma, to extensively Ox-LDL using capillary electrophoresis (cITP). The cITP was a suitable tool for evaluating the degree of oxidation of LDL for analyzing the optimal conditions for the oxidation of LDL by CuSO(4) to obtain LDL that was oxidized to a degree comparable to that in human plasma. In addition, both minimally and extensively Ox-LDL induced similar levels of ERK1/2 activation through Lox-1 in human coronary artery smooth muscle cells. These results indicate that both minimally and extensively Ox-LDL may be important for the progression of plaque growth through Lox-1. Since most previous reports have provided data only using extensively Ox-LDL, a re-evaluation is needed to analyze several signals that use LDL which has been oxidized to various degrees.
Tanigawa
Hiroyuki
H
Department of Cardiology, Fukuoka University Hospital, Fukuoka, Japan.
Miura
Shin-Ichiro
S
Zhang
Bo
B
Uehara
Yoshinari
Y
Matsuo
Yoshino
Y
Fujino
Masahiro
M
Sawamura
Tatsuya
T
Saku
Keijiro
K
D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D019075:Electrophoresis, Capillary; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D008077:Lipoproteins, LDL / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D010084:Oxidation-Reduction; D051127:Scavenger Receptors, Class E / Q000378:metabolism*
D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; D048052:Mitogen-Activated Protein Kinase 3