Apoptosis and expression of Bax protein and Fas antigen in glomeruli of a remnant-kidney model.
The role of apoptosis in glomerular cell depletion associated with a decrease in renal function is still controversial. To examine the involvement of apoptosis in renal disease, the occurrence of apoptosis during the progression of renal insufficiency as well as the expression of Bax protein and Fas antigen that are related to the apoptosis were investigated using five-sixths nephrectomized rats, one of the progressive renal disease models. Serum creatinine was significantly elevated to a level approximately five-fold higher than that in the sham-operated group on day 1 after the five-sixths nephrectomy and then maintained at a level approximately two- to three-fold higher until day 56 and then elevated further to a level eight-fold higher on day 96 after nephrectomy as compared with the sham-operated group. The total number of glomerular cells was significantly increased from day 7 to day 56 after nephrectomy and then returned to the level of the sham-operated group by day 96. The number of PCNA-positive cells (a marker of proliferating cells) in the glomeruli was significantly increased from day 7 to day 28 after nephrectomy; the highest level was observed on day 7, and the numbers then decreased gradually. Apoptotic cells, which were represented by TUNEL-positive cells, as well as apoptotic bodies were persistently increased with time after nephrectomy in the glomeruli of nephrectomized rats; apoptotic cells could hardly be observed in the sham-operated group. Therefore, glomerular cell proliferation appeared to begin immediately after nephrectomy and to continue until day 28 at a level high enough to overcome the decrease in the number of glomerular cells due to apoptosis, since the total number of glomerular cells was apparently high until day 56. On day 96, the decrease in the number of glomerular cells probably becomes predominant over cell proliferation, since apoptosis continuously increased with time after nephrectomy. The events on day 96 may be associated with the severely decreased renal function which was represented by the explosive increase in the serum creatinine level on the same day. The number of Fas antigen positive glomerular cells was increased from day 1 after nephrectomy and reached a plateau on day 21. The number of Bax protein positive glomerular cells was generally increased with time after nephrectomy, but the number was slightly decreased on day 21. The theory that the expression of Bax protein is correlated with apoptosis appears to fit the case of progressive renal disease. These results suggest that apoptosis is involved in the cell depletion of progressive renal insufficiency.
Hattori
T
T
New Drug Research Department, Tsumura Central Research Laboratories, Ibaraki, Japan.
Shindo
S
S
Kawamura
H
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001710:Biotin; D002452:Cell Count; D002455:Cell Division / Q000502:physiology; D003404:Creatinine / Q000097:blood; D053938:DNA Fragmentation; D003856:Deoxyuracil Nucleotides; D004195:Disease Models, Animal; D007674:Kidney Diseases / Q000378:metabolism / Q000601:surgery; D007678:Kidney Glomerulus / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009392:Nephrectomy; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000032:analysis / Q000096:biosynthesis*
C494828:Bax protein, rat; D003856:Deoxyuracil Nucleotides; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D001710:Biotin; D003404:Creatinine