Autologous extracellular cytochrome c is an endogenous ligand for leucine-rich alpha2-glycoprotein and beta-type phospholipase A2 inhibitor.
Beta-type phospholipase A(2) inhibitory protein (PLIbeta) from the serum of the venomous snake Gloydius brevicaudus neutralizes basic phospholipase A(2) (PLA(2)) from its own venom, and it has 33% sequence homology with human leucine-rich alpha(2)-glycoprotein (LRG), which has been recently reported to bind cytochrome c (Cyt c) (Cummings, C., Walder, J., Treeful, A., and Jemmerson, R. (2006) Apoptosis 11, 1121-1129). In the present study, PLIbeta was found to bind Cyt c. The interactions of LRG and PLIbeta with Cyt c were compared by surface plasmon resonance analysis. Human LRG bound horse and snake Cyt c with dissociation constants of 1.58 x 10(-13) M and 1.65 x 10(-10) M, respectively, but did not bind yeast Cyt c, while G. brevicaudus PLIbeta bound horse, snake, and yeast Cyt c with dissociation constants of 1.05 x 10(-10) M, 2.37 x 10(-12) M, and 1.67 x 10(-6) M, respectively. On the other hand, LRG did not show any PLA(2) inhibitory activity and did not bind G. brevicaudus basic PLA(2), whereas PLIbeta bound the basic PLA(2) with a dissociation constant of 1.21 x 10(-9) M, which is smaller than those with the Cyt c described above. The PLA(2) inhibitory activity of PLIbeta was also found to be suppressed by the binding of Cyt c to PLIbeta. These results suggest that autologous Cyt c is an endogeneous ligand for LRG and PLIbeta and that these serum proteins neutralize the autologous Cyt c released from the dead cells.
Shirai
Ryoichi
R
Laboratory of Biochemistry, Osaka University of Pharmaceutical Sciences, Nasahara, Takatsuki, Osaka 569-1094, Japan.
Gotou
Rikiya
R
Hirano
Fumiyasu
F
Ikeda
Kiyoshi
K
Inoue
Seiji
S
D000818:Animals; D001798:Blood Proteins / Q000737:chemistry*; D002942:Circular Dichroism; D045304:Cytochromes c / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005656:Fungal Proteins / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006736:Horses; D006801:Humans; D007930:Leucine / Q000235:genetics*; D008024:Ligands; D054467:Phospholipases A2 / Q000737:chemistry; D011485:Protein Binding; D012911:Snakes; D020349:Surface Plasmon Resonance
D001798:Blood Proteins; D005656:Fungal Proteins; D006023:Glycoproteins; C015246:LRG1 protein, human; D008024:Ligands; C400481:PLIalpha; D045304:Cytochromes c; D054467:Phospholipases A2; D007930:Leucine