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Published on: February 14, 2020

Methylglyoxal mediates vascular inflammation via JNK and p38 in human endothelial cells

Hideyuki Yamawaki1, Kazuaki Saito, Muneyoshi Okada

  • 1Dept. of Veterinary Pharmacology, Kitasato University., Towada, Aomori 034-8628, Japan. yamawaki@vmas.kitasato-u.ac.jp

American Journal of Physiology. Cell Physiology
|October 10, 2008
PubMed

Insights

Methylglyoxal (MGO), a glucose metabolite elevated in diabetes, causes vascular endothelial cell (EC) damage. MGO triggers inflammatory responses via JNK and p38 pathways, but these pathways do not mediate MGO-induced cell damage.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Vascular Biology

Background:

  • Methylglyoxal (MGO) is a reactive glucose metabolite.
  • Elevated plasma MGO is observed in diabetic patients.
  • MGO is implicated in diabetes-associated vascular endothelial cell (EC) injury and atherosclerosis.

Purpose of the Study:

  • To investigate the effects of MGO treatment on human umbilical vein ECs.
  • To examine MGO's impact on EC morphology and inflammatory responses.

Main Methods:

  • Treatment of human umbilical vein ECs with varying concentrations of MGO (0-420 microM) for different durations (20 min to 24 h).
  • Assessment of EC morphology, cyclooxygenase-2 (COX-2) mRNA and protein expression, PGE(2) release, and MAP kinase (JNK, p38, ERK) and NF-kappaB activation.
  • Utilized JNK and p38 inhibitors (SP600125, SB203580) and a superoxide dismutase/catalase mimetic (EUK134) to elucidate pathways.

Main Results:

  • MGO induced concentration-dependent cytotoxic morphological changes in ECs.
  • MGO upregulated COX-2 expression and PGE(2) release in a concentration- and time-dependent manner.
  • MGO activated JNK and p38 MAP kinases but not ERK or NF-kappaB; JNK and p38 inhibition prevented COX-2 induction, but not morphological damage.

Conclusions:

  • MGO mediates JNK- and p38-dependent inflammatory responses in ECs, potentially independent of oxidative stress.
  • MGO-induced morphological cell damage appears to be independent of the COX-2/PGE(2) pathway.

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