title: Minocycline attenuates both OGD-induced HMGB1 release and HMGB1-induced cell death in ischemic neuronal injury in PC12 cells.
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.
authors.affiliation: Department of Advanced Therapeutics, Division of Laboratory and Vascular Medicine, Field of Cardiovascular and Respiratory Disorders, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Ko-ichi
authors.initials: K
authors.lastname: Kawahara
authors.forename: Kamal Krishna
authors.initials: KK
authors.lastname: Biswas
authors.forename: Takashi
authors.initials: T
authors.lastname: Ito
authors.forename: Salunya
authors.initials: S
authors.lastname: Tancharoen
authors.forename: Yoko
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Matsuda
authors.forename: Yoko
authors.initials: Y
authors.lastname: Oyama
authors.forename: Kazunori
authors.initials: K
authors.lastname: Takenouchi
authors.forename: Naoki
authors.initials: N
authors.lastname: Miura
authors.forename: Noboru
authors.initials: N
authors.lastname: Arimura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nawa
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Meng
authors.forename: Binita
authors.initials: B
authors.lastname: Shrestha
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Arimura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iwata
authors.forename: Kentaro
authors.initials: K
authors.lastname: Mera
authors.forename: Hisayo
authors.initials: H
authors.lastname: Sameshima
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Ohno
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Maenosono
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tajima
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Uchikado
authors.forename: Terukazu
authors.initials: T
authors.lastname: Kuramoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakayama
authors.forename: Minoru
authors.initials: M
authors.lastname: Shigemori
authors.forename: Teruto
authors.initials: T
authors.lastname: Hashiguchi
authors.forename: Ikuro
authors.initials: I
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002070:Butadienes / Q000494:pharmacology; D002417:Cattle; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007511:Ischemia / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008911:Minocycline / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009570:Nitriles / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D009570:Nitriles; C113580:U 0126; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D008911:Minocycline; D005947:Glucose; D010100:Oxygen