Elsevier

Kidney International

Volume 63, Issue 3, March 2003, Pages 947-957
Kidney International

Cell Biology – Immunology – Pathology
Methylglyoxal induces apoptosis through activation of p38 mitogen-activated protein kinase in rat mesangial cells

https://doi.org/10.1046/j.1523-1755.2003.00829.xGet rights and content
Under an Elsevier user license
open archive

Methylglyoxal induces apoptosis through activation of p38 mitogen-activated protein kinase in rat mesangial cells.

Background

The formation of methylglyoxal (MG), a highly reactive dicarbonyl compound, is accelerated through several pathways, including the glycation reaction under diabetic conditions, presumably contributing to tissue injury in diabetes. On the other hand, apoptotic cell death of glomerular cells has been suggested to play a role in the development of glomerulosclerosis in various types of glomerular injuries. We therefore examined whether MG was capable of inducing apoptosis in rat mesangial cells to address the possible mechanism by which hyperglycemia-related products accelerated pathologic changes in diabetic glomerulosclerosis.

Methods

Rat mesangial cells were incubated with 0 to 400 μmol/L MG, followed by the detection of apoptosis by both TUNEL method and electrophoretic analysis for DNA fragmentation. In addition, we investigated intracellular mechanisms mediating MG-induced apoptosis, focusing especially on the p38 mitogen-activated protein kinase (MAPK) pathway.

Results

MG induced apoptosis in rat mesangial cells in a dose-dependent manner and was accompanied by the activation of p38α isoform. Aminoguanidine and N-acetyl-l-cysteine inhibited the MG-induced p38 MAPK activation, as well as apoptosis in rat mesangial cells, suggesting the involvement of oxidative stress in these phenomena. SB203580, a specific inhibitor of p38 MAPK also suppressed the MG-induced apoptosis in rat mesangial cells.

Conclusions

These results suggest a potential role for MG in glomerular injury through p38 MAPK activation under diabetic conditions and may serve as a novel insight into the therapeutic strategies for diabetic nephropathy.

Keywords

methylglyoxal
mesangial cells
apoptosis
glycation
p38 MAPK
diabetic nephropathy

Cited by (0)