Immuno-proteasome subunit LMP7 is up-regulated in the ischemic kidney in an experimental model of renovascular hypertension.
Immuno-proteasome is thought to be responsible for the processing of intracellular antigens and is induced when cells are treated with the inflammatory cytokines promoting cellular immunity. We tested the possibility that immuno-proteasome can be up-regulated in renal cells exposed to a long-lasting ischemia and inflammation in an experimental model of two-kidney, one-clip renovascular hypertension in the rat. Western blotting showed that immuno-proteasome subunit, LMP7, was up-regulated in the clipped ischemic kidney that was atrophic, but not in the contralateral unclipped kidney that underwent compensatory hypertrophy. Immunohistochemical analysis revealed that LMP7 was highly expressed in cortical epithelial and endothelial cells of the ischemic kidney. Surprisingly, the second immuno-subunit, LMP2, was almost undetectable, indicating that renal ischemia may induce exclusively the LMP7 subunit. We also found that renal ischemia neither reduced the SDS-stimulated proteasomal activity nor affected a high level of the PA28 activator. Thus, the results provide evidence that LMP7 immuno-subunit is induced in renal cells exposed to a long-lasting renal ischemia and inflammation, and that there is a direct link between LMP induction and renal atrophy. This opens an opportunity to study a role for LMP-containing proteasomes in the kidneys and other organs undergoing reduction in mass in diseases accompanied by a long-lasting ischemia and inflammatory responses.
Ostrowska
Halina
H
Department of Biology, Medical University of Bialystok, Kilinskiego 1, Bialystok 15-089, Poland. osthal@amb.edu.pl
Kruszewski
Kamil
K
Kasacka
Irena
I
D000818:Animals; D004195:Disease Models, Animal; D006978:Hypertension, Renovascular / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D007511:Ischemia / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D007668:Kidney / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D008297:Male; D009097:Multienzyme Complexes / Q000032:analysis / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D021122:Protein Subunits / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D015854:Up-Regulation
D009097:Multienzyme Complexes; C506159:PA28 protein, rat; D021122:Protein Subunits; D012967:Sodium Dodecyl Sulfate; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex