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Title: Minocycline attenuates both OGD-induced HMGB1 release and HMGB1-induced cell death in ischemic neuronal injury in PC12 cells
Authors: Kiyoshi Kikuchi
Ko ichi Kawahara
Kamal Krishna Biswas
Takashi Ito
Salunya Tancharoen
Yoko Morimoto
Fumiyo Matsuda
Yoko Oyama
Kazunori Takenouchi
Naoki Miura
Noboru Arimura
Yuko Nawa
Xiaojie Meng
Binita Shrestha
Shinichiro Arimura
Masahiro Iwata
Kentaro Mera
Hisayo Sameshima
Yoshiko Ohno
Ryuichi Maenosono
Yoshihiro Yoshida
Yutaka Tajima
Hisaaki Uchikado
Terukazu Kuramoto
Kenji Nakayama
Minoru Shigemori
Teruto Hashiguchi
Ikuro Maruyama
Division of Laboratory and Vascular Medicine
Omuta City General Hospital
Mahidol University
Kagoshima University Faculty of Medicine
Faculty of Medicine
Faculty of Agriculture
Kurume University School of Medicine
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 24-Jul-2009
Citation: Biochemical and Biophysical Research Communications. Vol.385, No.2 (2009), 132-136
Abstract: High mobility group box-1 (HMGB1), a non-histone DNA-binding protein, is massively released into the extracellular space from neuronal cells after ischemic insult and exacerbates brain tissue damage in rats. Minocycline is a semisynthetic second-generation tetracycline antibiotic which has recently been shown to be a promising neuroprotective agent. In this study, we found that minocycline inhibited HMGB1 release in oxygen-glucose deprivation (OGD)-treated PC12 cells and triggered the activation of p38mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases (ERK1/2). The ERK kinase (MEK)1/2 inhibitor U-0126 and p38MAPK inhibitor SB203580 blocked HMGB1 release in response to OGD. Furthermore, HMGB1 triggered cell death in a dose-dependent fashion. Minocycline significantly rescued HMGB1-induced cell death in a dose-dependent manner. In light of recent observations as well as the good safety profile of minocycline in humans, we propose that minocycline might play a potent neuroprotective role through the inhibition of HMGB1-induced neuronal cell death in cerebral infarction. © 2009 Elsevier Inc. All rights reserved.
ISSN: 10902104
Appears in Collections:Scopus 2006-2010

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