title: Metformin prevents methylglyoxal-induced apoptosis of mouse Schwann cells.
abstract: Methylglyoxal (MG) is involved in the pathogenesis of diabetic complications via the formation of advanced glycation end products (AGEs) and reactive oxygen species (ROS). To clarify whether the antidiabetic drug metformin prevents Schwann cell damage induced by MG, we cultured mouse Schwann cells in the presence of MG and metformin. Cell apoptosis was evaluated using Hoechst 33342 nuclear staining, caspase-3 activity, and c-Jun-N-terminal kinase (JNK) phosphorylation. Intracellular ROS formation was determined by flow cytometry, and AMP-activated kinase (AMPK) phosphorylation was also examined. MG treatment resulted in blunted cell proliferation, an increase in the number of apoptotic cells, and the activation of caspase-3 and JNK along with enhanced intracellular ROS formation. All of these changes were significantly inhibited by metformin. No significant activation of AMPK by MG or metformin was observed. Taken together, metformin likely prevents MG-induced apoptotic signals in mouse Schwann cells by inhibiting the formation of AGEs and ROS.
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Ota
authors.forename: Jiro
authors.initials: J
authors.lastname: Nakamura
authors.forename: Weiguo
authors.initials: W
authors.lastname: Li
authors.forename: Mika
authors.initials: M
authors.lastname: Kozakae
authors.forename: Atsuko
authors.initials: A
authors.lastname: Watarai
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Nakamura
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasuda
authors.forename: Eirtaro
authors.initials: E
authors.lastname: Nakashima
authors.forename: Keiko
authors.initials: K
authors.lastname: Naruse
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Watabe
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oiso
authors.forename: Yoji
authors.initials: Y
authors.lastname: Hamada
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D008687:Metformin / Q000008:administration & dosage*; D051379:Mice; D011765:Pyruvaldehyde / Q000008:administration & dosage*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012583:Schwann Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*
chemical_list: D004338:Drug Combinations; D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D011765:Pyruvaldehyde; D008687:Metformin