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Pediatric Nephrology

, Volume 21, Issue 5, pp 619–626 | Cite as

Nitric oxide and superoxide in rat mesangial cells: modulation by C-reactive protein

  • Howard TrachtmanEmail author
  • Stephen Futterweit
  • Christopher Arzberger
  • Jessica Bod
  • Judah Goldschmiedt
  • Haddassah Gorman
  • Krishna Reddy
  • Nicholas Franki
  • Pravin C. Singhal
Original Article

Abstract

Background: C-reactive protein (CRP) has been linked to cardiovascular and renal disease. We evaluated the effects of CRP on the production of nitric oxide (NO) and superoxide by rat mesangial cells (RMC) and the impact on cell function. Methods and Results: RMC were incubated with cytokines (IFN-γ, IL-1β, and LPS) and CRP (10–100 μg/ml) for 24–72 h. Exposure to CRP resulted in a time- and dose-dependent reduction in NO accumulation (p<0.05). Although inducible nitric oxide synthase (iNOS) protein expression was unaltered after 48 h, CRP stimulated expression of HSP90. Steady state abundance of iNOS mRNA increased nearly threefold after a 24-h exposure to CRP. Incubation with 100 μg/ml CRP for 60–120 min resulted in a 272% increase in superoxide production that was prevented by diphenyleneiodium chloride but not L-NAME (p<0.0001). Conclusion: CRP enhances superoxide release in RMC, which in turn inactivates NO and reduces net production. The functional relevance of these CRP-induced changes is supported by increased expression of HSP90 in RMC exposed to the mediator. These findings suggest that systemic inflammation, which contributes to the pathogenesis of atherosclerosis, may play a role in the progression of kidney disease.

Keywords

C-reactive protein Heat shock protein 90 Inducible nitric oxide synthase NADPH oxidase Nitric oxide Superoxide Rat mesangial cells 

Abbreviations

CRP

C-reactive protein

DPI

Diphenyleneiodium chloride

HSP

Heat shock protein

INOS

Inducible nitric oxide synthase

NO

Nitric oxide

RMC

Rat mesangial cell

Notes

Acknowledgements

This work was supported in part by a grant from the National Institute of Health, NIDDK, RO1-52147 (HT). Portions of this work have been presented at the annual meetings of the Society for Pediatric Research, May 5, 2002 and the American Society of Nephrology, November 3, 2002, and have been published in abstract form (Pediatr Res 2002;51:428A and J Am Soc Nephrol 2002;13:556A).

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Copyright information

© IPNA 2006

Authors and Affiliations

  • Howard Trachtman
    • 1
    • 2
    • 3
    Email author
  • Stephen Futterweit
    • 1
    • 2
  • Christopher Arzberger
    • 1
    • 2
  • Jessica Bod
    • 1
    • 2
  • Judah Goldschmiedt
    • 1
    • 2
  • Haddassah Gorman
    • 1
    • 2
  • Krishna Reddy
    • 1
    • 2
  • Nicholas Franki
    • 1
    • 2
  • Pravin C. Singhal
    • 1
    • 2
  1. 1.Department of Pediatrics (Division of Nephrology)Schneider Children’s HospitalNew Hyde ParkUSA
  2. 2.Department of Medicine (Division of Nephrology), Long Island Jewish Hospital, North Shore-Long Island Jewish Health SystemLong Island Campus for the Albert Einstein College of MedicineNew Hyde ParkUSA
  3. 3.Division of NephrologySchneider Children’s HospitalNew Hyde ParkUSA

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