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- Title
Cytochrome c-induced lymphocyte death from the outside in: inhibition by serum leucine-rich alpha-2-glycoprotein-1.
- Authors
Codina, Ramil; Vanasse, Amelia; Kelekar, Ameeta; Vezys, Vaiva; Jemmerson, Ronald
- 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.
- Publication
Apoptosis : an international journal on programmed cell death, 2010, Vol 15, Issue 2, p139
- ISSN
1573-675X
- Publication type
Journal Article
- DOI
10.1007/s10495-009-0412-0