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Updated: Aug 24, 2026

Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells
Published on: March 16, 2017
Advanced glycosylation end products induce inducible nitric oxide synthase (iNOS) expression via a p38 MAPK-dependent
Po-Chiao Chang1, Tso-Hsiao Chen, Chun-Jen Chang
1Graduate Institute of Biomedical Technology, Taipei Medical University, Taipei, Taiwan.
Background:
Advanced glycosylation end products (AGEs) accumulation in tissue has been implicated in diabetic related complications, including diabetic nephropathy. Activation of peroxisome proliferator activated receptor-gamma (PPAR-gamma) ameliorates diabetic nephropathy.
Methods:
In the present study, we investigated the effects of AGEs on inducible nitric oxide synthase (iNOS) expression and nitric oxide production, and the effects of rosiglitazone, an activator of PPAR-gamma, on AGE-induced iNOS expression and nitrite release in glomerular mesangial cells.
Results:
AGEs caused a dose- and time-dependent increase of iNOS induction and nitrite accumulation in mesangial cells. A protein tyrosine kinase inhibitor (genistein), or a p38 mitogen-activated protein kinase (MAPK) inhibitor (SB203580) suppressed AGE-induced iNOS expression and nitrite release from mesangial cells. Addition of bovine serum albumin (BSA)-AGEs to mesangial cells increased p38 MAPK activities. Activation of PPAR-gamma by rosiglitazone inhibited AGE-induced iNOS expression, nitrite release, and p38 MAPK activation in mesangial cells. AGE-stimulated nitrite release was attenuated by pretreatment with anti-tumor necrosis factor-alpha (TNF-alpha) and anti-transforming growth factor-beta (TGF-beta) antibodies. AGE-induced iNOS expression was inhibited by treatment with a nuclear factor-kappaB (NF-kappaB) inhibitor, pyrrolidone dithiocarbamate. Addition of BSA-AGEs to mesangial cells stimulated p65 NF-kappaB translocation from the cytosol to the nucleus.
Conclusion:
These data suggest that cytokine release, NF-kappaB and p38 MAPK-dependent pathways may play a role in AGE-induced iNOS expression and subsequent nitric oxide production in mesangial cells. Rosiglitazone may prevent AGE-induced iNOS expression by interfering with p38 MAPK activity.
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