Selective vulnerability of spinal motor neurons to reactive dicarbonyl compounds, intermediate products of glycation, in vitro: implication of inefficient glutathione system in spinal motor neurons.
We investigated the effects of two reactive dicarbonyl compounds, methylglyoxal (MG) and 3-deoxyglucosone (3-DG), on cultured spinal cord neurons. Incubation of cortical and spinal neurons with MG and 3-DG for 24 h induced neuronal death in a dose-dependent manner. Spinal motor neurons were more vulnerable than spinal non-motor neurons and cortical neurons. Treatments with glutathione (GSH)-augmenting agents showed protective effects against MG and 3-DG neurotoxicity. Motor neurons were better protected than non-motor neurons. Cotreatment, but not pretreatment, of aminoguanidine (AG), a known inhibitor of advanced glycation end-products (AGEs) from crosslinking, showed a protective effect on spinal neurons with no difference in protective rates between motor and non-motor spinal neurons. Treatments with GSH depleting agents enhanced the neurotoxicity of MG and 3-DG on spinal neurons. Motor neurons were more vulnerable than non-motor neurons with GSH-depleting treatments prior to MG and 3-DG exposures. These data demonstrate that spinal motor neurons are more vulnerable to dicarbonyl compounds, and this selectivity might be related to the relatively inefficient GSH system in spinal motor neurons.
Shinpo
K
K
Department of Neurology, Hokkaido University School of Medicine, Kita 14 Nishi 5 Kita-ku, Sapporo, Japan. kshinpo@med.hokudai.ac.jp
Kikuchi
S
S
Sasaki
H
H
Ogata
A
A
Moriwaka
F
F
Tashiro
K
K
D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism; D011765:Pyruvaldehyde / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D006146:Guanidines; D011765:Pyruvaldehyde; D003847:Deoxyglucose; C016350:3-deoxyglucosone; D005978:Glutathione; C004479:pimagedine