Methylglyoxal Induces Apoptosis through Oxidative Stress-Mediated Activation of p38 Mitogen-Activated Protein Kinase in Rat Schwann Cells

: Although recent studies have suggested the potential involvement of apoptotic cell death in the development of diabetic neuropathy, the precise mechanism remains to be elucidated. On the other hand, it is known that the formation of methylglyoxal (MG), a highly reactive dicarbonyl compound, is acc...

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Bibliographic Details
Published in:Annals of the New York Academy of Sciences 2005-06, Vol.1043 (1), p.151-157
Main Authors: FUKUNAGA, MICHIRU, MIYATA, SATOSHI, HIGO, SATOMI, HAMADA, YASUHIRO, UEYAMA, SHIGEMITSU, KASUGA, MASATO
Format: Article
Language:English
Subjects:
Acetylcysteine - pharmacology
Animals
Antioxidants - pharmacology
apoptosis
Apoptosis - drug effects
diabetic neuropathy
Enzyme Activation
glutathione
glycation
methylglyoxal
Oxidative Stress - drug effects
Oxidative Stress - physiology
p38 mitogen-activated protein kinase
p38 Mitogen-Activated Protein Kinases - metabolism
Phosphorylation
Pyruvaldehyde - pharmacology
Rats
Schwann cells
Schwann Cells - drug effects
Schwann Cells - enzymology
Schwann Cells - physiology
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Summary:: Although recent studies have suggested the potential involvement of apoptotic cell death in the development of diabetic neuropathy, the precise mechanism remains to be elucidated. On the other hand, it is known that the formation of methylglyoxal (MG), a highly reactive dicarbonyl compound, is accelerated under diabetic conditions through several glucose‐related metabolisms including the glycation reaction. We found that MG was capable of inducing apoptosis in peripheral nerve‐derived Schwann cells (SCs) in a time‐ and dose‐dependent manner, accompanied by a reduction of intracellular glutathione content. Furthermore, MG induced phosphorylation of MKK3/MKK6, an upstream molecule in the p38 MAPK pathway. N‐acetyl‐L‐cysteine, an antioxidant, successfully suppressed the activity of the p38 MAPK signaling pathway along with the inhibition of apoptosis, indicating the involvement of oxidative stress in the MG‐induced apoptosis via the p38 MAPK pathway. These results suggest a possible contribution of glucose‐derived MG to the development of diabetic neuropathy by injuring the cellular constituent of the peripheral nerve system, such as SCs, in the hyperglycemic milieu.
ISSN:0077-8923
1749-6632
DOI:10.1196/annals.1333.019