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Your search keyword '"Nozawa, Yoshinori"' showing total 19 results
Start Over Author "Nozawa, Yoshinori" Journal bioorganic & medicinal chemistry
19 results on '"Nozawa, Yoshinori"'

19. A novel kavalactone derivative protects against H2O2-induced PC12 cell death via Nrf2/ARE activation

Author

Tanaka, Arisa, Hamada, Nanako, Fujita, Yasunori, Itoh, Tomohiro, Nozawa, Yoshinori, Iinuma, Munekazu, and Ito, Masafumi

Subjects
*ANTIOXIDANTS, *LACTONES, *NEURODEGENERATION, *CELL death, *HYDROGEN peroxide, *OXIDATIVE stress, *ENZYME activation, *KAVA plant, *THERAPEUTICS
Abstract

Abstract: Oxidative stress is involved in the pathogenesis of neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases. Natural kavalactones isolated from Piper methysticum (Piperaceae) are capable of activating the Nrf2/ARE (antioxidant response element) pathway and thus enhancing the expression of phase II antioxidant enzymes such as heme oxygenase-1 (HO-1). In an attempt to identify kavalactone derivatives that are more potent in Nrf2/ARE activation than natural compounds, we synthesized a series of chemically-modified kavalactones and studied their effects on the ARE enhancer activity in rat pheochromocytoma PC12 cells. Among 81 compounds tested, a kavalactone derivative, 2′,6′-dichloro-5-methoxymethyl-5,6-dehydrokawain [(E)-6-(2′,6′-dichlorostyryl)-4-methoxy-5-(methoxymethyl)-2H-pyran-2-one] (1), exhibited the strongest ARE enhancer activity. The ARE activation and HO-1 protein induction by the compound 1 were higher than those by natural kavalactones. The compound did not affect cell viability and induced expression of various phase II enzymes. Nuclear translocation of Nrf2 after treatment with 1 was preceded by phosphorylation of ERK1/2 and p38. The compound transiently increased intracellular ROS levels. Finally, pretreatment with the compound ameliorated H2O2-induced cell death, which was associated with increased expression of HO-1. These results suggest that the compound 1 protects against oxidative stress-induced neuronal cell death via a preconditioning effect on the Nrf2/ARE activation. [Copyright &y& Elsevier]

Published
2010
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