Kiyoshi KikuchiKo ichi KawaharaKamal Krishna BiswasTakashi ItoSalunya TancharoenYoko MorimotoFumiyo MatsudaYoko OyamaKazunori TakenouchiNaoki MiuraNoboru ArimuraYuko NawaXiaojie MengBinita ShresthaShinichiro ArimuraMasahiro IwataKentaro MeraHisayo SameshimaYoshiko OhnoRyuichi MaenosonoYoshihiro YoshidaYutaka TajimaHisaaki UchikadoTerukazu KuramotoKenji NakayamaMinoru ShigemoriTeruto HashiguchiIkuro MaruyamaDivision of Laboratory and Vascular MedicineOmuta City General HospitalMahidol UniversityKagoshima University Faculty of MedicineFaculty of MedicineFaculty of AgricultureKurume University School of Medicine2018-09-132018-09-132009-07-24Biochemical and Biophysical Research Communications. Vol.385, No.2 (2009), 132-136109021040006291X2-s2.0-67349138648https://repository.li.mahidol.ac.th/handle/20.500.14594/27175High 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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1016/j.bbrc.2009.04.041