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Induction of neurite outgrowth by α-phenyl-N-tert-butylnitrone through nitric oxide release and Ras-ERK pathway in PC12 cells

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Title: Induction of neurite outgrowth by α-phenyl-N-tert-butylnitrone through nitric oxide release and Ras-ERK pathway in PC12 cells
Authors: Yasui, Hironobu Browse this author →KAKEN DB
Ito, Nozomi Browse this author
Yamamori, Tohru Browse this author →KAKEN DB
Nakamura, Hideo Browse this author →KAKEN DB
Okano, Jun Browse this author
Asanuma, Taketoshi Browse this author
Nakajima, Takayuki Browse this author
Kuwabara, Mikinori Browse this author
Inanami, Osamu Browse this author →KAKEN DB
Keywords: Antioxidant
neurogenesis
nitric oxide
Issue Date: Jun-2010
Publisher: Informa Healthcare
Journal Title: Free Radical Research
Volume: 44
Issue: 6
Start Page: 645
End Page: 654
Publisher DOI: 10.3109/10715761003692537
PMID: 20370559
Abstract: It has previously been suggested that the spin trap agent α-phenyl-N-tert-butylnitrone (PBN) induces neurite outgrowth through activation of the Ras-ERK pathway in PC12 cells. However, the chemical properties of PBN contributing to its biological function and the detailed mechanism for the activation of Ras by PBN remain unknown. This study demonstrates that the hydrophobic structure of PBN is related to the activation of Ras, by comparing with hydrophilic analogues of PBN. [14C]-labelled PBN was found to localize in the lipid fraction and activate Ras indirectly. On the other hand, neurite outgrowth by PBN was inhibited by a nitric oxide (NO) scavenger. Moreover, the neurite outgrowth induced by PBN and the NO donor NOR4 was inhibited by the dominant negative Ras or MAPK/ERK inhibitor. Taken together, these results suggest that PBN is incorporated into the plasma membrane and induces neurite outgrowth in PC12 cells by activating the Ras-ERK pathway through NO release
Type: article (author version)
URI: http://hdl.handle.net/2115/46751
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 稲波 修

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