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Effects of protein oxidation on the structure and stability of model discoidal high-density lipoproteins

Shobini Jayaraman1, Donald L Gantz, Olga Gursky

  • 1Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts 02118, USA. shobini@bu.edu

Biochemistry
|February 28, 2008
PubMed

Insights

Oxidation of high-density lipoprotein (HDL) proteins destabilizes their structure, accelerating remodeling and fusion. This impacts HDL function and atherosclerosis prevention.

Area of Science:

  • Biochemistry
  • Lipid Metabolism
  • Cardiovascular Research

Background:

  • High-density lipoproteins (HDLs) are crucial for preventing atherosclerosis by facilitating reverse cholesterol transport.
  • Oxidative modifications to HDL proteins and lipids can alter their function through complex mechanisms.
  • Understanding the specific impact of protein oxidation is key to elucidating HDL's role in cardiovascular health.

Purpose of the Study:

  • To investigate the effects of selective protein oxidation on the structure, stability, and remodeling of discoidal HDLs.
  • To differentiate the roles of oxidative modifications in HDL proteins versus lipids.
  • To elucidate the mechanisms by which protein oxidation impacts HDL assembly and function.

Main Methods:

  • Reconstitution of discoidal HDLs using human apolipoproteins (A-I, A-II, C-I) and phosphatidylcholines.
  • Selective protein oxidation using hypochlorite (HOCl).
  • Analysis of structural changes via gel electrophoresis and electron microscopy.
  • Assessment of thermal denaturation, stability, and remodeling using far-UV circular dichroism and light scattering.

Main Results:

  • Protein oxidation induced remodeling of discoidal HDLs into larger and smaller particles at ambient temperatures.
  • Oxidation destabilized HDL structure, accelerating protein unfolding, dissociation, and lipoprotein fusion.
  • Reduced protein-lipid affinity and apolipoprotein cross-linking were identified as key mechanisms driving destabilization.

Conclusions:

  • Oxidation of HDL proteins significantly destabilizes HDL disk assembly.
  • Protein oxidation accelerates HDL remodeling and fusion, impacting overall lipoprotein function.
  • These findings extend to plasma spherical HDLs, offering insights into the complex effects of oxidation on lipoproteins in vivo.

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