Stress associated proteins metallothionein, HO-1 and HSP 70 in human zero-hour biopsies of transplanted kidneys.
Light microscopic alterations reflecting both previous and preservation-induced changes in the donor organ are usually not very distinctive. The ischemia/reperfusion-associated injury depends primarily on the conditions of donor organ preservation. The present study examined human kidney biopsies with special attention paid to the molecular mechanisms of preservation-induced injury preceding reperfusion. Stress-associated proteins hemeoxygenase-1 (HO-1), heat shock protein 70 (HSP 70), and metallothionein (MT) were studied in human zero-hour biopsies of transplanted kidneys prior to reperfusion in 29 patients. Protein expression was evaluated by semiquantitative immunohistochemistry and Western blotting for HO-1 and HSP 70. These findings were correlated with terminal deoxynucleotidyltransferase-mediated 2'-deoxyuridine 5'-triphosphate-digoxigenin nick end labeling (TUNEL) staining and follow up. Compared to controls, MT and HSP 70 expression was significantly higher at zero hour. In contrast, HO-1 and the number of TUNEL-positive cells were not elevated. MT and HO-1 immunoexpression were inversely associated with graft function, and hence, were of prognostic relevance. MT and HSP 70 were sensitive to the duration of cold ischemia. MT and HO-1 are suitable indicators for tissue injury during ischemia and may serve as new predictive markers that need to be validated in further independent studies.
August
Christian
C
Institute of Pathology, Muenster University Hospital, University of Muenster, Muenster, Germany. augustc@uni-muenster.de
Brockmann
Jens
J
Vowinkel
Thorsten
T
Wolters
Heiner
H
Dietl
Karl-Heinz
KH
Levkau
Bodo
B
Heidenreich
Stefan
S
Lang
Detlef
D
Baba
Hideo A
HA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001706:Biopsy; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis*; D051547:Heme Oxygenase-1 / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000737:chemistry* / Q000473:pathology; D016030:Kidney Transplantation; D008668:Metallothionein / Q000032:analysis; D008875:Middle Aged
D018840:HSP70 Heat-Shock Proteins; D008668:Metallothionein; D051547:Heme Oxygenase-1