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Expression of MnSOD and Bcl‐2 is elevated in the mouse renal medulla.
Author(s) -
Zhou Xiaoming,
Ferraris Joan D.,
Burg Maurice B.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a451-c
Subject(s) - oxidative stress , reactive oxygen species , superoxide dismutase , chemistry , kidney , protein carbonylation , cytosol , medulla , superoxide , oxidative phosphorylation , microbiology and biotechnology , biology , biochemistry , enzyme , endocrinology , oxidative damage
High NaCl and urea increase reactive oxygen species (ROS) of mitochondrial origin and cause oxidative damage to proteins and DNA in cell culture. Also, kidney medullas of normal mice have oxidative stress as indicated by high protein carbonylation. To understand how the kidney cells adapt to oxidative stress, we measured expression of antioxidant proteins. Superoxide dismutase (SOD) lowers the ROS, superoxide, by converting it to H2O2. We found that in vivo protein expression of MnSOD (the mitochondrial SOD) increases progressively between cortex, outer medulla (OM) and inner medulla (IM). Further, water restriction increases it in all three regions. In cultures of mIMCD3 cells, high NaCl, but not high urea, increases MnSOD protein expression. To understand the relationship between oxidative stress and MnSOD in the kidney, we measured its enzymatic activity. The activity of MnSOD per unit of its protein, is lower in IM than in cortex and, following water restriction, it falls in all regions of the kidney. We suggest that high NaCl reduces MnSOD activity, and that MnSOD protein abundance increases in compensation. In contrast to MnSOD, protein expression of neither Cu/ZnSOD (the cytosolic SOD), or thioredoxin I (a co‐enzyme predominantly located in cytosol) is higher in the medulla than in the cortex, and neither changes significantly with water restriction. The anti‐apoptotic and anti‐oxidant protein Bcl‐2 often acts in concert with MnSOD to prevent oxidative injury to cells. Bcl‐2 protein abundance is higher in the renal medulla than in the cortex, but water restriction does not affect its expression in any of these regions. In conclusion, expression of MnSOD and Bcl‐2 proteins is elevated in the renal medulla, which may contribute to survival of its cells despite hyperosmolality‐induced oxidative stress.