title: Minocycline reduces oxygen-glucose deprivation-induced PC12 cell cytotoxicity via matrix metalloproteinase-9, integrin β1 and phosphorylated Akt modulation.
abstract: Minocycline has shown anti-inflammatory, anti-apoptotic, and antioxidative activities in many models of cerebral ischemia and human acute ischemic stroke. However, the cellular and molecular bases for its neuroprotective effects have not been fully elucidated. In this study, we investigated whether pre-treatment with minocycline could attenuate oxygen-glucose deprivation-induced PC12 cytotoxicity. The activity of matrix metalloproteinase-9 was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis zymography. And the expressions of integrin β1, Akt and phosphorylated Akt were analyzed by Western blot. Our results showed that minocycline could ameliorate oxygen-glucose deprivation-induced PC12 cell cytotoxicity at concentrations of 20 nM-20 μM, down-regulate the production and activity of matrix metalloproteinase-9, inhibit the degradation of integrin β1, and up-regulate Akt phosphorylation at optimal concentration of 200 nM. The results may provide a new area for minocycline's therapeutic intervention for improving the outcomes of cerebral ischemia.
authors.affiliation: Department of Neurology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, Guangdong, China. xiaohongchenzssy@yahoo.com.cn
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Chen
authors.forename: Shaoqiong
authors.initials: S
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.forename: Cansheng
authors.initials: C
authors.lastname: Zhu
authors.forename: Aimin
authors.initials: A
authors.lastname: Wu
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Ma
authors.forename: Fuhua
authors.initials: F
authors.lastname: Peng
authors.forename: Lili
authors.initials: L
authors.lastname: Ma
authors.forename: Dongliang
authors.initials: D
authors.lastname: Zhu
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Rongbiao
authors.initials: R
authors.lastname: Pi
mesh_terms: D000818:Animals; D016923:Cell Death; D005947:Glucose / Q000172:deficiency; D019012:Integrin beta1 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008911:Minocycline / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D016716:PC12 Cells; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats
chemical_list: D019012:Integrin beta1; D018696:Neuroprotective Agents; D051057:Proto-Oncogene Proteins c-akt; D020780:Matrix Metalloproteinase 9; D008911:Minocycline; D005947:Glucose; D010100:Oxygen