Heme oxygenase 1 expression in young uremic patients on hemodialysis.
Oxidative stress plays an important role in the cardiovascular complications in end-stage renal disease (ESRD) patients on long-term hemodialysis (HD). Heme oxygenase-1 (HO-1) inhibits inflammatory events and protects against oxidative stress and endothelial injury. Therefore, we followed the effects of single HD sessions on HO-1 expression. A competitive reverse transcriptase PCR method was used to estimate HO-1 induction before and immediately after HD and 48 h later in 17 young uremic patients. We also measured the concentrations of plasma hemoglobin and bilirubin as indicators of hemolysis, the ferroxidase activity, and the erythrocyte-derived reduced and oxidized glutathione levels as oxidative stress markers, and the homocysteine levels as an independent risk factor. We found significant differences in HO-1 expression patterns in the patients, depending on the duration of HD treatment. Short-term HD [ n=7, median 19 months (9, 29 quartiles)] resulted in an elevated HO-1 expression, which was not further upregulated during HD. Long-term HD [ n=10, median 97 months (53, 150 quartiles)] led to downregulation of baseline HO-1 expression in ESRD patients. In these patients, a single HD session results in erythrocyte injury and a transient one- to five-fold elevation of HO-1 expression. The chronic downregulation of the baseline expression of HO-1 in long-term HD patients resulted in recurring oxidative stress during each HD session, which may contribute to accelerate the progression of atherosclerosis.
Maróti
Zoltán
Z
Department of Pediatrics, University of Szeged, Korányi fasor 14-15, 6725 Szeged, Hungary. zmaroti@pedia.szote.u-szeged.hu
Németh
Ilona
I
Túri
Sándor
S
Karg
Eszter
E
Ugocsai
Péter
P
Endreffy
Emoke
E
D000328:Adult; D001663:Bilirubin / Q000097:blood; D002570:Ceruloplasmin / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005978:Glutathione / Q000097:blood; D019803:Glutathione Disulfide / Q000097:blood; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D006454:Hemoglobins / Q000032:analysis; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D006435:Renal Dialysis / Q000009:adverse effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014511:Uremia / Q000628:therapy*
D006454:Hemoglobins; D012333:RNA, Messenger; D006710:Homocysteine; D006419:Heme Oxygenase (Decyclizing); D002570:Ceruloplasmin; D005978:Glutathione; D001663:Bilirubin; D019803:Glutathione Disulfide