Different protein expression in normal and dysfunctional platelets from uremic patients.
Although many uremic patients show platelet dysfunctionality, there are others with normal platelet functionality and even with thrombotic tendencies. Our aim was to evaluate changes in the expression of proteins in functional and dysfunctional uremic platelets. Using the platelet function analyzer (PFA-100) assay, uremic patients were divided according to their platelet functionality into normal (n=7) and dysfunctional (n=8). There were no significant differences in the number of circulating platelets and hematocrit and hemoglobin levels. Two-dimensional electrophoresis and mass spectrometry were used to determine and identify changes in protein expression. The closure time (CT) in the PFA-100 assay was significantly prolonged in the dysfunctional uremic platelets. In the dysfunctional platelets, actin-interacting protein-1 isotype 1 was down-regulated, while integrin IIb was up-regulated. Glutathione-S-transferase isotypes 1 and 2 and peroxiredoxin VI were up-regulated in the dysfunctional platelets. Pearson analysis showed a negative correlation between the platelet expression of integrin IIb and creatinine clearance. A positive correlation was found between creatinine clearance and glutathione-S-transferase isotype 2. Serum uric acid concentration was positively correlated with CT values and glutathione-S-transferase isotype 1. In conclusion, the analysis of the protein expression in uremic platelets with normal and dysfunctional activity revealed differences which may occur at the megakaryocyte level.
Marques
María
M
Nephrology Department, Hospital Clínico San Carlos, Universidad Complutense, Madrid, Spain.
Sacristán
Daniel
D
Mateos-Cáceres
Petra J
PJ
Herrero
José
J
Arribas
María J
MJ
González-Armengol
Juan J
JJ
Villegas
Ana
A
Macaya
Carlos
C
Barrientos
Alberto
A
López-Farré
Antonio J
AJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D018821:CD18 Antigens / Q000097:blood; D002450:Cell Communication / Q000502:physiology; D003404:Creatinine / Q000097:blood; D003599:Cytoskeleton / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D005982:Glutathione Transferase / Q000097:blood; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D054465:Peroxiredoxin VI / Q000097:blood; D040901:Proteomics; D014511:Uremia / Q000097:blood* / Q000503:physiopathology*; D014527:Uric Acid / Q000097:blood
D001798:Blood Proteins; D018821:CD18 Antigens; D008840:Microfilament Proteins; C115237:actin interacting protein 1; D014527:Uric Acid; D003404:Creatinine; D054465:Peroxiredoxin VI; D005982:Glutathione Transferase