Acatalasemia sensitizes renal tubular epithelial cells to apoptosis and exacerbates renal fibrosis after unilateral ureteral obstruction.
Tissue homeostasis is determined by the balance between oxidants and antioxidants. Catalase is an important antioxidant enzyme regulating the level of intracellular hydrogen peroxide and hydroxyl radicals. The effect of catalase deficiency on renal tubulointerstitial injury induced by unilateral ureteral obstruction (UUO) has been studied in homozygous acatalasemic mutant mice (C3H/AnLCs(b)Cs(b)) compared with wild-type mice (C3H/AnLCs(a)Cs(a)). Complete UUO caused interstitial cell infiltration, tubular dilation and atrophy, and interstitial fibrosis with accumulation of type IV collagen in obstructed kidneys (OBK) of both mouse groups. However, the degree of injury showed a significant increase in OBK of acatalasemic mice compared with that of wild-type mice until day 7. The deposition of lipid peroxidation products including 4-hydroxy-2-hexenal, malondialdehyde, and 4-hydroxy-2-nonenal was severer in dilated tubules of acatalasemic OBK. Apoptosis in tubular epithelial cells significantly increased in acatalasemic OBK at day 4. Expression of caspase-9, a marker of mitochondrial pathway-derived apoptosis, increased in dilated tubules of acatalasemic mice. The level of catalase activity remained low in acatalasemic OBK until day 7 without compensatory upregulation of glutathione peroxidase activity. The data indicate that acatalasemia exacerbated oxidation of renal tissue and sensitized tubular epithelial cells to apoptosis in OBK of UUO. This study demonstrates that catalase deficiency enhanced tubulointerstitial injury and fibrosis in a murine model of UUO and thus supports the protective role of catalase in this model.
Sunami
Reiko
R
Okayama Univ. Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Sugiyama
Hitoshi
H
Wang
Da-Hong
DH
Kobayashi
Mizuho
M
Maeshima
Yohei
Y
Yamasaki
Yasushi
Y
Masuoka
Noriyoshi
N
Ogawa
Norio
N
Kira
Shohei
S
Makino
Hirofumi
H
D020642:Acatalasia / Q000503:physiopathology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D002374:Catalase / Q000235:genetics; D004847:Epithelial Cells / Q000502:physiology*; D005355:Fibrosis; D005979:Glutathione Peroxidase / Q000502:physiology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007684:Kidney Tubules / Q000166:cytology* / Q000473:pathology / Q000502:physiology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009395:Nephritis, Interstitial / Q000473:pathology; D009929:Organ Size / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014517:Ureteral Obstruction / Q000150:complications / Q000473:pathology*; D014969:Xanthine Oxidase / Q000502:physiology
D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D014969:Xanthine Oxidase