Methylglyoxal induces apoptosis through activation of p38 MAPK in rat Schwann cells.
The formation of glucose-derived methylglyoxal (MG), a highly reactive dicarbonyl compound, is accelerated under diabetic conditions. We examined whether MG was capable of inducing apoptosis in Schwann cells (SCs), since recent studies have suggested a potential involvement of apoptotic cell death in the development of diabetic neuropathy. MG induced apoptosis in SCs in a dose-dependent manner, accompanied by a reduction of intracellular glutathione content and activation of the p38 MAPK. Inhibiting the p38 MAPK activation by SB203580 successfully suppressed the MG-induced apoptosis in SCs. Aminoguanidine and N-acetyl-L-cysteine also inhibited the MG-induced p38 MAPK activation and apoptosis along with restoration of the intracellular glutathione content. These results suggest a potential role for MG in SC injury through oxidative stress-mediated p38 MAPK activation under diabetic conditions, and it may serve as a novel insight into therapeutic strategies for diabetic neuropathy.
Fukunaga
Michiru
M
Division of Diabetes, Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Miyata
Satoshi
S
Liu
Bing Fen
BF
Miyazaki
Hiroyuki
H
Hirota
Yushi
Y
Higo
Satomi
S
Hamada
Yasuhiro
Y
Ueyama
Shigemitsu
S
Kasuga
Masato
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D008657:Metabolic Clearance Rate; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D011765:Pyruvaldehyde / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D012584:Sciatic Nerve / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D011765:Pyruvaldehyde; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases