LC-MS/MS analysis of carboxymethylated and carboxyethylated phosphatidylethanolamines in human erythrocytes and blood plasma.
An amino group of phosphatidylethanolamine (PE) is considered as a target for nonenzymatic glycation, and the potential involvement of lipid glycation in the pathogenesis of diabetic complications has generated interest. However, unlike an early glycation product of PE (Amadori-PE), the occurrence and roles of advanced glycation end products of PE (AGE-PE) in vivo have been unclear. Here, we developed an LC-MS/MS method for the analysis of AGE-PE [carboxymethyl-PE (CM-PE) and carboxyethyl-PE (CE-PE)]. Collision-induced dissociation of CM-PE and CE-PE produced characteristic ions, permitting neutral loss scanning (NLS) and multiple reaction monitoring (MRM) of AGE-PE. By NLS analysis, a series of AGE-PE molecular species was detected in human erythrocytes and blood plasma. In LC-MS/MS analysis, MRM enabled the separation and determination of the predominant AGE-PE species. Between healthy subjects and diabetic patients, no significant differences were observed in AGE-PE concentrations in erythrocytes and plasma, whereas Amadori-PE concentrations were higher in diabetic patients. These results provide direct evidence for the presence of AGE-PE in human blood, and indicated that, compared with Amadori-PE, AGE-PE is less likely to be accumulated in diabetic blood. The presently developed LC-MS/MS method appears to be a powerful tool for understanding in vivo lipid glycation and its pathophysiological consequence.
Shoji
Naoki
N
Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan.
Nakagawa
Kiyotaka
K
Asai
Akira
A
Fujita
Ikuko
I
Hashiura
Aya
A
Nakajima
Yasushi
Y
Oikawa
Shinichi
S
Miyazawa
Teruo
T
D001774:Blood Chemical Analysis / Q000379:methods*; D016022:Case-Control Studies; D002853:Chromatography, Liquid / Q000379:methods*; D003920:Diabetes Mellitus / Q000097:blood / Q000378:metabolism; D004912:Erythrocytes / Q000737:chemistry*; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010714:Phosphatidylethanolamines / Q000097:blood* / Q000378:metabolism*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult
D017127:Glycation End Products, Advanced; D010714:Phosphatidylethanolamines; C483858:phosphatidylethanolamine
J Lipid Res. 2007 Dec;48(12):2779-87
17848584
Diabetes Obes Metab. 2007 May;9(3):233-45
17391149
Arch Biochem Biophys. 2001 Jul 15;391(2):245-54
11437356
Free Radic Biol Med. 1989;7(2):209-17
2806945
Biophys Chem. 1999 Aug 30;80(3):165-77
17030324
J Lipid Res. 2006 May;47(5):964-74
16470027
Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6434-8
8341651
Biochemistry. 1995 Mar 21;34(11):3702-9
7893666
Eur J Biochem. 1998 Aug 1;255(3):685-9
9738908
J Lipid Res. 2002 Mar;43(3):523-9
11893788
J Lipid Res. 1992 Jul;33(7):1051-9
1431584
J Biol Chem. 1997 Jul 11;272(28):17473-9
9211892
FEBS Lett. 1996 Feb 26;381(1-2):77-81
8641444
Methods Enzymol. 2000;312:32-45
11070861
Biochem J. 2008 Nov 15;416(1):145-52
18564061
J Lipid Res. 2005 Nov;46(11):2514-24
16150834
Curr Drug Metab. 2006 Jun;7(5):541-5
16787161
Carbohydr Res. 2000 Apr 20;325(3):157-68
10795806
Arterioscler Thromb Vasc Biol. 2000 Feb;20(2):467-77
10669645
Bioorg Med Chem. 2000 Jan;8(1):115-21
10968270
J Biol Chem. 1957 May;226(1):497-509
13428781
Biosci Biotechnol Biochem. 1998 May;62(5):893-901
9648220
Rapid Commun Mass Spectrom. 2004;18(24):3123-30
15565732
J Agric Food Chem. 2000 Apr;48(4):1000-8
10775341
FEBS Lett. 2000 Sep 8;481(1):26-30
10984609
J Biol Chem. 1995 Apr 28;270(17):10017-26
7730303
Life Sci. 1995;57(9):873-9
7630316
J Lipid Res. 2005 Feb;46(2):373-82
15520455
Anal Biochem. 1999 Jul 15;272(1):48-55
10405292
J Biol Chem. 1999 Jun 4;274(23):16494-500
10347212
J Lipid Res. 1965 Jul;6:428-31
14336214
FEBS Lett. 2003 Dec 4;555(2):419-23
14644453