Low-density lipoprotein oxidized to various degrees activates ERK1/2 through Lox-1

Atherosclerosis. 2006 Oct;188(2):245-50. doi: 10.1016/j.atherosclerosis.2005.10.046. Epub 2005 Dec 27.


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.

Publication types

  • Comparative Study

MeSH terms

  • Cell Communication / physiology*
  • Cells, Cultured
  • Electrophoresis, Capillary
  • Enzyme Activation / physiology
  • Humans
  • Immunoblotting
  • Lipoproteins, LDL / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Muscle, Smooth, Vascular / cytology
  • Oxidation-Reduction
  • Scavenger Receptors, Class E / metabolism*


  • Lipoproteins, LDL
  • OLR1 protein, human
  • Scavenger Receptors, Class E
  • oxidized low density lipoprotein
  • Mitogen-Activated Protein Kinase 3