Influence of ischaemia/reperfusion and LFA-1 inhibition on telomere lengths and CDKI genes in ex vivo haemoperfusion of primate kidneys.
The telomere (T) length, p21(WAF1/CIP1) and p27(Kip1) cyclin-dependent kinase inhibitor (CDKI) genes are the markers of cell senescence and DNA damage. The aim of the study was to determine the influence of renal ischaemia/reperfusion (I/R) and anti-lymphocyte function-associated antigen-1 (LFA-1) monoclonal antibody (mAb) treatment on the value of the above-mentioned markers. Significantly higher levels of p21 and p27 were expressed by the glomeruli (P=0.001 and P=0.0001), tubules (P=0.0065 and P=0.0006), and interstitial cells (P=0.0017 and P=0.0022, respectively) of the xenoperfused kidneys. The mean T length of non-perfused renal specimens (5.56+/-0.60 kbp) was longer than that of the xenoperfused kidneys (5.46+/-0.36 kbp) [P= non-significant (NS)]. Addition of anti-LFA-1 mAb did not significantly influence the gene expression profile in the xenoperfused kidneys. The mean T length was longer in the kidneys with anti-LFA-1 mAb than in those without the medication (5.7+/-0.11 vs 5.13+/-0.31 kbp) (P=0.0661). Kidney I/R is associated with telomere shortening and an over-expression of p21 and p27 CDKIs, which indicates substantial DNA damage and/or accelerated tissue senescence. Although anti-LFA-1 mAb had some protective effect on the telomeres, it did not influence the gene expression profile in this study.
Chkhotua
Archil B
AB
National Centre of Urology, Tsinandali St. 9, 380044, Tbilisi, Georgia. achkotua@hotmail.com
Schelzig
Hubert
H
Wiegand
Peter
P
Grosse
Stephan
S
Reis
Simone
S
Art
Martina
M
Abendroth
Dietmar
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015870:Gene Expression; D006464:Hemoperfusion; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism*; D008252:Macaca fascicularis; D015427:Reperfusion Injury / Q000235:genetics* / Q000473:pathology*; D016615:Telomere / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016169:Lymphocyte Function-Associated Antigen-1; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27