Carboxymethylated phosphatidylethanolamine in mitochondrial membranes of mammals--evidence for intracellular lipid glycoxidation.
The non-enzymatic modification of aminophospholipids with lipoperoxidation-derived aldehydes and glycoxidation-derived products have been reported previously. However, it remains unknown whether intracellular membranes are damaged by these glycoxidation-derived products. To investigate this issue, we tested whether aminophospholipids from mitochondrial membranes are damaged by glycoxidative stress the mitochondrion being identified as the major site of reactive-species production in the cell. We have used a selected-ion-monitoring/gas-chromatography/mass-spectrometry assay for carboxymethylethanolamine (CM-Etn) detection, and provide evidence for the presence of CM-Etn in mitochondrial phospholipids. Further, as a physiological approach to evaluate the influence of mitochondrial oxidative stress in CM-Etn formation, we also present the comparative levels of CM-Etn in mitochondrial membranes of ten mammalian species ranging in maximum life-span from 3.5 years to 100, since the rate of mitochondrial reactive-oxygen-species production is inversely correlated to the maximum life-span. Our results show that CM-Etn levels correlate in a logarithmic fashion with the maximum-life-span [[CM-Etn] = 0.51 + 0.50 x', where x' = log(maximum-life-span); r = 0.81, P < 0.004]. The data demonstrate the intracellular occurrence of glycoxidative processes affecting membrane lipids. Moreover, these data show that longer-lived mammals contain higher levels of CM-Etn in mitochondrial membrane aminophospholipids. This trend could result from differences in rates of CM-Etn accumulation and/or phospholipid turnover.
Pamplona
R
R
Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, Spain.
Requena
J R
JR
Portero-Otín
M
M
Prat
J
J
Thorpe
S R
SR
Bellmunt
M J
MJ
D000818:Animals; D002417:Cattle; D006224:Cricetinae; D004285:Dogs; D006168:Guinea Pigs; D006736:Horses; D006801:Humans; D008563:Membrane Lipids / Q000032:analysis*; D051379:Mice; D008928:Mitochondria / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000032:analysis* / Q000737:chemistry; D011817:Rabbits; D012756:Sheep; D013552:Swine
D008563:Membrane Lipids; D010714:Phosphatidylethanolamines