Metformin prevents methylglyoxal-induced apoptosis of mouse Schwann cells.
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.
Ota
Kimiko
K
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Nakamura
Jiro
J
Li
Weiguo
W
Kozakae
Mika
M
Watarai
Atsuko
A
Nakamura
Nobuhisa
N
Yasuda
Yutaka
Y
Nakashima
Eirtaro
E
Naruse
Keiko
K
Watabe
Kazuhiko
K
Kato
Koichi
K
Oiso
Yutaka
Y
Hamada
Yoji
Y
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*
D004338:Drug Combinations; D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D011765:Pyruvaldehyde; D008687:Metformin