title: Reduced cell replication and induction of apoptosis by advanced glycation end products in rat Schwann cells.
abstract: We investigated the effects of advanced glycation end products (AGEs) derived from glucose, glyceraldehyde, and glycolaldehyde (designated as AGE-1, -2, and -3, respectively) on the viability, replication rate, and cytokine production of cultured Schwann cells. AGE-2 and -3, but not AGE-1, induced apoptosis, and significantly decreased the viability measured by MTT assay. The decrease was prevented completely by antioxidant alpha-lipoic acid and was prevented partially by p38 mitogen-activated protein kinase inhibitor SB202190. The decrease in mitochondrial membrane potential by AGE-2 and -3 was also observed. In addition, AGE-2 and -3 significantly suppressed the replication rate as shown by reduced bromodeoxyuridine uptake, whereas they enhanced the release of TNF-alpha and IL-1beta into the medium and activated nuclear factor-kappaB. The effects of AGE-1 on these measures were equivocal. The series of events elicited by AGE-2 and -3 may be responsible for some of the aspects of pathogenetic mechanisms in patients with diabetic neuropathy.
authors.affiliation: Drug Development Research Laboratories, Sanwa Kagaku Kenkyusho Co., Ltd., Inabe, Japan. h_sekido@skk-net.com
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sekido
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Takahito
authors.initials: T
authors.lastname: Jomori
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Chihiro
authors.initials: C
authors.lastname: Yabe-Nishimura
authors.forename: Soroku
authors.initials: S
authors.lastname: Yagihashi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D016207:Cytokines; D017127:Glycation End Products, Advanced; D016328:NF-kappa B