Nitric oxide modulates mechanical strain-induced activation of p38 MAPK in mesangial cells

A. J. Ingram, Leighton R James, K. Thai, H. Ly, L. Cai, J. W. Scholey

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Mesangial cells (MC), grown on extracellular matrix (ECM) protein-coated plates and stretched, proliferate and produce ECM, recapitulating in vivo responses to increased glomerular capillary pressure (Pgc). Transduction of strain involves mitogen-activated protein kinases (MAPK), and we have shown that p38 MAPK is activated by strain in MC. Because in vivo studies show that nitric oxide (NO) in the remnant kidney limits glomerular injury without reducing Pgc, we studied whether NO attenuated stretch-induced p38 activation in MC. Increasing p38 activation occurred with increasing stretch, maximally at 10 min at -27-kPa vacuum. Cyclic strain increased nuclear translocation of phosphorylated p38 by immunofluorescent microscopy and nuclear protein binding to nuclear factor-κB (NF-κB) consensus sequences by mobility shift assay. Both events were largely abrogated by the p38 inhibitor SB-203580. The NO donors 3-morpholin-osydnonimine, S-nitroso-N-acetylpenicillamine, and 8-bromoguanosine 3',5'-cyclic monophosphate, a stable cGMP analog, prevented p38 activation and nulcear translocation. Thus strain induces p38 activity and translocation to the nucleus and p38-dependent increases in nuclear protein binding to NF-κB. This pathway is attenuated by the NO donors or a cGMP analog.

Original languageEnglish (US)
Pages (from-to)F243-F251
JournalAmerican Journal of Physiology - Renal Physiology
Volume279
Issue number2 48-2
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • Kidney glomerulus
  • Mitogen-activated protein kinases
  • Nuclear factor-κB
  • Physical forces
  • Signaling

ASJC Scopus subject areas

  • Physiology
  • Urology

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