Hydrogen peroxide downregulates IL-1-driven mesangial iNOS activity

Implications for glomerulonephritis

Edgar A. Jaimes, Karl A. Nath, Leopoldo Raij

Research output: Contribution to journalArticle

Abstract

In glo-merulonephritides, autacoids such as nitric oxide (NO), reactive oxygen species, and prostanoids are produced in increased amounts in response to cytokines such as interleukin-1 (IL-1). These autacoids influence the expression of glomerular injury by their direct as well as interactive actions. We studied the effect of hydrogen peroxide (H2O2) on NO production in rat mesangial cells. We demonstrate that transient exposure of mesangial cells to H2O2 prior to sustained exposure to IL-1 decreased extracellular accumulation of NO2/NO3 and cellular guanosine 3′,5′-cyclic monophosphate (cGMP) content. H2O2 markedly impaired inducible nitric oxide synthase (iNOS) activity induced by IL-1 directly measured by the conversion of L-f14C]arginine to L-[14C]citrulline. Such impairment in iNOS activity was accompanied by a parallel reduction in iNOS protein abundance but not by a reduced expression of iNOS mRNA. The inhibitory effect of H2O2 on NOS activity was further supported by peroxide-induced impairment in IL-1-driven, NO-dependent synthesis of prostaglandin E2. Our studies thus provide the first direct evidence of a posttranscriptional inhibitory effect of H2O2 on iNOS activity. Additionally, our studies uncover the existence of a previously unrecognized effect of H2O2 on the production of NO that may exert influence on the severity of glomerular injury during glomerular inflammation.

Original languageEnglish
JournalAmerican Journal of Physiology
Volume272
Issue number6 PART 2
StatePublished - Dec 1 1997
Externally publishedYes

Fingerprint

Nitric Oxide Synthase Type II
Glomerulonephritis
Interleukin-1
Hydrogen Peroxide
Down-Regulation
Nitric Oxide
Autacoids
Mesangial Cells
Citrulline
Guanosine
Peroxides
Wounds and Injuries
Dinoprostone
Prostaglandins
Arginine
Reactive Oxygen Species
Cytokines
Inflammation
Messenger RNA
Proteins

Keywords

  • Glomerulonephritis
  • Mesangium
  • Nitric oxide
  • Prostanoids

ASJC Scopus subject areas

  • Physiology (medical)

Cite this

Hydrogen peroxide downregulates IL-1-driven mesangial iNOS activity : Implications for glomerulonephritis. / Jaimes, Edgar A.; Nath, Karl A.; Raij, Leopoldo.

In: American Journal of Physiology, Vol. 272, No. 6 PART 2, 01.12.1997.

Research output: Contribution to journalArticle

Jaimes, Edgar A. ; Nath, Karl A. ; Raij, Leopoldo. / Hydrogen peroxide downregulates IL-1-driven mesangial iNOS activity : Implications for glomerulonephritis. In: American Journal of Physiology. 1997 ; Vol. 272, No. 6 PART 2.
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