CV-2619 protects cultured astrocytes against reperfusion injury via nerve growth factor production.
In this study, we examined the effect of the neuroprotective agent 2, 3-dimethoxy-5-methyl-6-(10-hydroxydecyl)-1,4-benzoquinone (CV-2619) on reperfusion injury in cultured rat astrocytes after exposure to hydrogen peroxide (H(2)O(2))-containing medium. CV-2619 (10 nM to 10 microM) significantly attenuated the reperfusion-induced decrease in cell viability. The compound showed an anti-apoptotic effect in this astrocyte injury model. Antioxidants such as ascorbic acid, alpha-tocopherol and reduced glutathione also inhibited H(2)O(2) exposure-induced cytotoxicity. CV-2619 did not affect the levels of reactive oxygen species, but it increased nerve growth factor (NGF) production. The effect of CV-2619 on H(2)O(2) exposure-induced cytotoxicity was blocked by cycloheximide and anti-NGF antibody. The protective effect of CV-2619 was antagonized by the mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase inhibitor 2'-amino-3'-methoxyflavone and the phosphatidylinositol-3 kinase inhibitor wortmannin. These findings suggest that the effect of CV-2619 is mediated at least partly by NGF production in astrocytes and that ERK and phosphatidylinositol-3 kinases play a role in the downstream mechanism.
Takuma
K
K
Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, 518 Arise, Ikawadani-cho, Nishi-ku, 651-2180, Kobe, Japan.
Yoshida
T
T
Lee
E
E
Mori
K
K
Kishi
T
T
Baba
A
A
Matsuda
T
T
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects*; D016227:Benzoquinones / Q000494:pharmacology*; D002478:Cells, Cultured; D020932:Nerve Growth Factor / Q000096:biosynthesis*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D014451:Ubiquinone / Q000031:analogs & derivatives
D000975:Antioxidants; D016227:Benzoquinones; D018696:Neuroprotective Agents; D014451:Ubiquinone; D020932:Nerve Growth Factor; C036619:idebenone