Fructose-induced peroxynitrite production is mediated by methylglyoxal in vascular smooth muscle cells.

Abstract

Methylglyoxal (MG), a highly reactive molecule, has been implicated in the development of insulin resistance. We investigated whether fructose, a precursor of MG, induced ONOO(-) generation and whether this process was mediated via endogenously increased MG formation. Fructose significantly increased MG generation in vascular smooth muscle cells (VSMCs) in a concentration and time dependent manner. The intracellular production of MG was increased by 153+/-23% or 259+/-28% after cells were treated 6 h with fructose (15 mM or 30 mM), compared with production from untreated cells (p<0.01, n=4 for each group). A significant increase in the production of ONOO(-), NO, and O(2)(*-), was found in the cells treated with fructose (15 mM) or MG (10 microM). Fructose- or MG-induced ONOO(-) generation was significantly inhibited by MG scavengers, including reduced glutathione or N-acetyl-l-cysteine, and by O(2)(*-) or NO inhibitors, such as diphenylene iodonium, superoxide dismutase or N-nitro-l-arginine methyl ester. Moreover, an enhanced iNOS expression was also observed in the cells treated directly with MG which was significantly inhibited when co-application with N-acetyl-l-cysteine. Our results demonstrated that fructose is capable of inducing a significant increase in ONOO(-) production, which is mediated by an enhanced formation of endogenous MG in VSMCs.

• Authors: Hui Wang, Qing H Meng, Tuanjie Chang, Lingyun Wu
• Journal: Life sciences (Life Sci) Vol. 79 Issue 26 Pg. 2448-54 (Nov 25 2006) ISSN: 0024-3205 [Print] Netherlands
• PMID: 16950408 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Superoxides
• Peroxynitrous Acid
• Fructose
• Nitric Oxide
• Pyruvaldehyde
• Nitric Oxide Synthase
• Superoxide Dismutase
• Glutathione
• NG-Nitroarginine Methyl Ester
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Animals
• Cell Line
• Dose-Response Relationship, Drug
• Enzyme Inhibitors (pharmacology)
• Fructose (pharmacology)
• Glutathione (pharmacology)
• Muscle, Smooth, Vascular (cytology, drug effects, metabolism)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Peroxynitrous Acid (biosynthesis)
• Pyruvaldehyde (metabolism)
• Superoxide Dismutase (pharmacology)
• Superoxides (metabolism)
• Time Factors