Enzymatic methyl esterification of erythrocyte membrane proteins is impaired in chronic renal failure. Evidence for high levels of the natural inhibitor S-adenosylhomocysteine.
The enzyme protein carboxyl methyltransferase type II has been recently shown to play a crucial role in the repair of damaged proteins. S-adenosylmethionine (AdoMet) is the methyl donor of the reaction, and its demethylated product, S-adenosylhomocysteine (AdoHcy), is the natural inhibitor of this reaction, as well as of most AdoMet-dependent methylations. We examined erythrocyte membrane protein methyl esterification in chronic renal failure (CRF) patients on conservative treatment or hemodialyzed to detect possible alterations of the methylation pattern, in a condition where a state of disrupted red blood cell function is present. We observed a significant reduction in membrane protein methyl esterification in both groups, compared to control. The decrease was particularly evident for cytoskeletal component ankyrin, which is known to be involved in membrane stability and integrity. Moreover, we observed a severalfold rise in AdoHcy levels, while AdoMet concentration was comparable to that detected in the control, resulting in a lower [AdoMet]/[AdoHcy] ratio (P < 0.001). Our findings show an impairment of this posttranslational modification of proteins, associated with high AdoHcy intracellular concentration in CRF. The data are consistent with the notion that, in CRF, structural damages accumulate in erythrocyte membrane proteins, and are not adequately repaired.
Chair of Nephrology/Department of Pediatrics, School of Medicine, Second University of Naples, Italy.
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Perna
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Ingrosso
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Zappia
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Galletti
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De Santo
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000201:enzymology*; D004951:Esterification; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008745:Methylation; D008875:Middle Aged; D008954:Models, Biological; D011497:Protein O-Methyltransferase / Q000378:metabolism*; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D014508:Urea / Q000097:blood
D008565:Membrane Proteins; D012436:S-Adenosylmethionine; D014508:Urea; D012435:S-Adenosylhomocysteine; D011497:Protein O-Methyltransferase