The Hierarchy of Structural Transitions Induced in Cytochrome C by Anionic Phospholipids Determines Its Peroxidase Activation and Selective Peroxidation During Apoptosis in Cells

Details

• Personal Author:
  Basova LV ; Bayir H ; Belikova NA ; Jiang J ; Kagan VE ; Kapralov AA ; Kurnikov IV ; Tyurin VA ; Tyurina YY ; Vladimirov YA ; Vlasova II ; Zhao Q
• Description:
  Activation of peroxidase catalytic function of cytochrome c (cyt c) by anionic lipids is associated with destabilization of its tertiary structure. We studied effects of several anionic phospholipids on the protein structure by monitoring (1) Trp59 fluorescence, (2) Fe-S(Met80) absorbance at 695 nm, and (3) EPR of heme nitrosylation. Peroxidase activity was probed using several substrates and protein-derived radicals. Peroxidase activation of cyt c did not require complete protein unfolding or breakage of the Fe-S(Met80) bond. The activation energy of cyt c peroxidase changed in parallel with stability energies of structural regions of the protein probed spectroscopically. Cardiolipin (CL) and phosphatidic acid (PA) were most effective in inducing cyt c peroxidase activity. Phosphatidylserine (PS) and phosphatidylinositol bisphosphate (PIP2) displayed a significant but much weaker capacity to destabilize the protein and induce peroxidase activity. Phosphatidylinositol trisphosphate (PIP3) appeared to be a stronger inducer of cyt c structural changes than PIP2, indicating a role for the negatively charged extra phosphate group. Comparison of cyt c-deficient HeLa cells and mouse embryonic cells with those expressing a full complement of cyt c demonstrated the involvement of cyt c peroxidase activity in selective catalysis of peroxidation of CL, PS, and PI, which corresponded to the potency of these lipids in inducing cyt c's structural destabilization. [Description provided by NIOSH]
• Subjects:
  Energy Metabolism Enzymes Lipids Occupational Health Safety
• Keywords:
  Cell-metabolism Cellular-structures Cellular-transport-mechanism Enzyme-activity Lipid-peroxidation Metabolism Oxidation Oxidation-reduction-reactions
• ISSN:
  0006-2960
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  46
• Issue:
  49
• NIOSHTIC Number:
  nn:20033313
• Citation:
  Biochemistry 2007 Dec; 46(49):14232-14244
• Contact Point Address:
  Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15260
• Federal Fiscal Year:
  2008
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Biochemistry
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6187e218b8fa900808a61102a635397f1c69afb73763214f6b7dce73b435d3839464c973da8bba6eb4e8cc230956ae0df01705c6152e7f4643eea877e3f7e9a8
• Download URL:
  https://stacks.cdc.gov/view/cdc/188941/cdc_188941_DS1.pdf
• File Type:
  [PDF - 478.31 KB ]