A Dibenzoylmethane Derivative Protects Against Hydrogen Peroxide-Induced Cell Death and Inhibits Lipopolysaccharide-Induced Nitric Oxide Production in Cultured Rat Astrocytes

作者：Takano K^*; Sugita K; Moriyama M; Hashida K; Hibino S; Choshi T; Murakami R; Yamada M; Suzuki H; Hori O; Nakamura Y

来源：Journal of Neuroscience Research, 2011, 89(6): 955-965.

DOI：10.1002/jnr.22617

• oxidative stress
• NO production
• astrocyte
• dibenzoylmethane

Activation of glia has been observed in various neurodegenerative diseases. Excessive production of nitric oxide (NO), as a consequence of increased inducible nitric oxide synthase (iNOS) in glia, contributes to the neurodegeneration. The enhancement of intracellular stresses such as oxidative stress and endoplasmic reticulum (ER) stress has been also implicated in several neurodegenerative disorders. During a search for compounds that regulate ER stress, a dibenzoylmethane derivative, 2,2'-dimethoxydibenzoylmethane (DBM 14-26), was identified as a novel neuroprotective agent (Takano et al. [2007] Am. J. Physiol. Cell Physiol. 293: C1884-C1894). In the present study, we found that DBM 14-26 protected cultured astrocytes from H(2)O(2)-induced cytotoxicity at lower concentrations than antioxidants, GSH and N-acetyl cysteine. DBM 14-26 prevented the production of reactive oxygen species in the cells exposed to H(2)O(2) as evaluated by fluorescent intensity of dichlorofluorescein. Further examination revealed that DBM 14-26 inhibited lipopolysaccharide (LPS)-induced iNOS expression and NO production. DBM 14-26 suppressed LPS-stimulated nuclear factor-kappa B (NF-kappa B) activation evaluated by p65 immunostaining and gel retardation electrophoresis. These results indicate that DBM 14-26 protects astrocytes from oxidative stress and suppresses astrocytes activation via inhibition of NF-kappa B activation. Functional regulation of astrocytes by DBM 14-26 could be a therapeutic candidate for the treatment of neurodegenerative diseases.

• 出版日期2011-6