Apoptosis

, Volume 15, Issue 2, pp 139–152

Cytochrome c-induced lymphocyte death from the outside in: inhibition by serum leucine-rich alpha-2-glycoprotein-1

  • Ramil Codina
  • Amelia Vanasse
  • Ameeta Kelekar
  • Vaiva Vezys
  • Ronald Jemmerson
Original Paper

Abstract

Previously we reported that serum leucine-rich alpha-2-glycoprotein-1 (LRG) binds cytochrome c (Cyt c; Cummings et al., Apoptosis 11:1121–1129, 2009). Here we show that LRG binding to Cyt c is similar to that of Apaf-1. LRG and Apaf-1 share partial amino acid sequences, compete for binding Cyt c, and are inhibited by modification at lysine 72 in Cyt c. However, in contrast to Apaf-1, LRG acts as a survival factor in vitro rather than a pro-apoptotic factor. By depleting LRG from culture medium we found that LRG protects against a toxic effect of exogenous Cyt c on lymphocytes that would otherwise result in an apoptotic phenotype. LRG, as well as antibodies specific for Cyt c, increased cell viability in the absence of added Cyt c indicating that Cyt c released by dying cells in the cultures is itself toxic. Protection from extracellular Cyt c-induced lymphotoxicity appears to involve an active mechanism rather than steric hindrance of Cyt c. Thus, serum LRG when bound to extracellular Cyt c that is released from apoptotic cells acts as a survival factor for lymphocytes and possibly other cells that are susceptible to the toxic effect of extracellular Cyt c.

Keywords

Cytochrome c Leucine-rich alpha-2-glycoprotein-1 Apoptosis Survival factor Apaf-1 

Supplementary material

10495_2009_412_MOESM1_ESM.doc (123 kb)
Supplementary material 1 (DOC 123 kb)

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Ramil Codina
    • 1
  • Amelia Vanasse
    • 1
  • Ameeta Kelekar
    • 2
  • Vaiva Vezys
    • 1
  • Ronald Jemmerson
    • 3
  1. 1.Department of MicrobiologyUniversity of Minnesota Medical SchoolMinneapolisUSA
  2. 2.Department of Laboratory Medicine and Pathology and Masonic Cancer CenterUniversity of Minnesota Medical SchoolMinneapolisUSA
  3. 3.Department of Microbiology, Masonic Cancer Center, and Center for ImmunologyUniversity of Minnesota Medical SchoolMinneapolisUSA

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