Send to

Choose Destination
See comment in PubMed Commons below
Kidney Int. 2004 Nov;66(5):1881-9.

Induction of antioxidant enzymes in murine podocytes precedes injury by puromycin aminonucleoside.

Author information

  • 1Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109, USA.



An imbalance between the generation of reactive oxygen species (ROS) and antioxidant defense mechanisms has been suggested to play an important role in podocyte injury in nephrotic syndrome. Experimental nephrotic syndrome induced by injection of puromycin aminonucleoside (PAN) into rats is a well-established model of nephrotic syndrome, and can be largely prevented by pretreatment with antioxidant enzymes (AOE), suggesting that podocyte injury may be mediated by ROS.


To test the hypothesis that PAN-induced podocyte injury is modulated in part by podocyte antioxidant defenses, we analyzed AOE activities, lipid peroxidation products, and relative ROS levels in podocytes using our recently reported in vitro model of PAN-induced podocyte injury.


PAN treatment induced early increases in both podocyte hydrogen peroxide and superoxide and later increases in lipid peroxidation products. Compared to baseline activities, PAN also induced significant changes in the major cellular AOE activities (maximum increases of 151% for catalase, 134% for superoxide dismutase, and 220% for glutathione peroxidase vs. time-matched controls). These changes largely preceded the development of extensive podocyte process retraction and actin filament disruption, which was maximal at 7 days.


These results demonstrate that (1) PAN treatment induces significant early changes in podocyte ROS, (2) podocytes can mount an antioxidant defense against oxidant stress, and (3) this protective response is initiated prior to the development of extensive oxidant-induced podocyte structural injury. These findings suggest that enhancement of podocyte AOE activities represent a potential therapeutic target to protect from or ameliorate podocyte injury during nephrotic syndrome.

[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk