Renal cell apoptosis in chronic obstructive uropathy: The roles of caspases

Renal cell apoptosis in chronic obstructive uropathy: The roles of caspases. Apoptosis of tubular and interstitial cells is well documented in kidneys with chronic obstructive uropathy (COU) and probably plays an important role in the pathogenesis of this condition. The molecular control of apoptosi...

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Bibliographic Details
Published in:Kidney international 2001-09, Vol.60 (3), p.924-934
Main Authors: Truong, Luan D., Choi, Yeong-Jin, Tsao, Chun Chui, Ayala, Gustavo, Sheikh-Hamad, David, Nassar, George, Suki, Wadi N.
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Atrophy
Biological and medical sciences
Caspases - genetics
Caspases - metabolism
cell death
cysteinyl aspartate-specific proteinase
Fibrosis
interstitial cell apoptosis
Isoenzymes - genetics
Isoenzymes - metabolism
kidney injury
Kidney Tubules - enzymology
Kidney Tubules - pathology
Male
Medical sciences
Mice
Mice, Inbred C57BL
Nephrology. Urinary tract diseases
Organ Size
RNA, Messenger - analysis
RNA, Messenger - metabolism
tubular cell apoptosis
Ureteral Obstruction - enzymology
Ureteral Obstruction - pathology
urinary obstruction
Urinary system involvement in other diseases. Miscellaneous
Urinary tract. Prostate gland
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Summary:Renal cell apoptosis in chronic obstructive uropathy: The roles of caspases. Apoptosis of tubular and interstitial cells is well documented in kidneys with chronic obstructive uropathy (COU) and probably plays an important role in the pathogenesis of this condition. The molecular control of apoptosis in COU remains poorly understood. Apoptosis in general is known to proceed initially along distinct pathways, which later converge into a common arm characterized by orderly activation of caspases. Caspases are cytosolic enzymes that belong to a 12-member family and serve as effector molecules for apoptosis. The role of individual caspases in mediating renal cell apoptosis in kidneys with COU is studied. Kidneys were harvested from sham-operated mice and mice with COU created by left ureter ligation at days 4, 7, 15, 20, and 30. The following studies were performed: (1) determination of dried kidney weight; (2) in situ end labeling of fragmented DNA to detect apoptotic tubular and interstitial cells; (3) ribonuclease protection assay with specific anti-sense RNA probes for caspases 1, 2, 3, 6, 7, 8, 9, 11, and 12 to detect the expression of individual caspases; (4) immunostaining for caspases; and (5) assay for caspase 3. To assess the role of caspases in COU-associated renal cell apoptosis, the frequencies of apoptotic tubular and interstitial cells were separately quantitated for each experimental time point, and their patterns of variation were correlated with those of individual caspases. The obstructed kidneys showed progressive tissue loss (60% of control at day 15). Apoptosis of both tubular and interstitial cells was seen in obstructed kidneys. Tubular cell apoptosis peaked at four days after ureter ligation (13-fold of control), remained high between days 4 to 15, and thereafter decreased rapidly. Apoptotic interstitial cells were scanty initially, but gradually increased throughout the entire experiment. Apoptosis was minimal throughout the experiment in control and contralateral kidneys. In control and contralateral kidneys, caspases 2, 3, 6, 7, 8, and 9 mRNAs were expressed at low levels, whereas those for caspases 1, 11, and 12 were not detected. The obstructed kidneys displayed increased expression of all tested caspases. Caspases 1, 11, and 12 mRNAs were detected in obstructed kidneys in a common pattern characterized by a sharp increase at day 4, followed by a decrease until day 20, and a subsequent sharp increase until the end of the study at
ISSN:0085-2538
1523-1755
DOI:10.1046/j.1523-1755.2001.060003924.x