In vivo activation of c-Jun N-terminal kinase signaling cascade prior to granule cell death induced by trimethyltin in the dentate gyrus of mice

Neuropharmacology
Kiyokazu OgitaY Yoneda

Abstract

The systemic administration of trimethyltin (TMT, 2.8 mg/kg, i.p.) induced granule cell death in the mouse dentate gyrus selectively 2 days later. The administration of TMT not only enhanced activator protein-1 DNA binding, along with an increase in expression of c-Jun and Fra-2, in the hippocampus 1 day later, but also facilitated phosphorylation of c-Jun N-terminal kinase (JNK) within the cytosol and nucleus. There was also a concomitant increase in the level of phosphorylated JNK kinase (MKK4/SEK1) in the cytosol 16-24 h after the administration. Moreover, TMT markedly elevated endogenous levels of both phosphorylated c-Jun and phosphorylated activating transcription factor-2 (ATF-2), in addition to activating JNK activity in the nuclear extracts obtained 16-24 h post-administration. Immunohistochemical analysis revealed that whereas Fra-2 and phosphorylated ATF-2 were expressed in the CA1 pyramidal cell layer predominantly, phosphorylated c-Jun was observed in both the CA1 pyramidal and dentate granule cell layers after TMT administration. Taken together, our data indicate that TMT activates the JNK pathway in the hippocampus prior to neuronal cell death. The prior activation of this pathway could be at least in part involv...Continue Reading

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Citations

Apr 21, 2009·Evidence-based Complementary and Alternative Medicine : ECAM·Noriko HattoriShoei Furukawa
Mar 3, 2007·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Norihito ShintaniAkemichi Baba
Mar 19, 2011·Neurochemistry International·Maria Concetta GelosoFabrizio Michetti
Dec 5, 2009·Neurochemistry International·Masanori YoneyamaKiyokazu Ogita
Jan 15, 2008·Neurochemistry International·Francesco MisitiFabrizio Michetti
Dec 10, 2009·Journal of Neuroscience Research·Masanori YoneyamaKiyokazu Ogita
Jun 6, 2006·Neuroscience Letters·Eishi FunakoshiFumiaki Ito
Dec 30, 2014·Oxidative Medicine and Cellular Longevity·Noemí Cárdenas-RodríguezLiliana Carmona-Aparicio
Jun 16, 2011·Neurochemistry International·Eun-Joo ShinHyoung-Chun Kim
Jun 22, 2010·Journal of Pharmacological Sciences·Reiko NagashimaKiyokazu Ogita
Sep 7, 2016·International Journal of Molecular Sciences·Sandeep Vasant MoreDong-Kug Choi
Mar 29, 2019·Journal of Cellular Physiology·Nafiseh FalsafiMehri Azadbakht
Aug 2, 2019·Biological & Pharmaceutical Bulletin·Hang Thi Nguyet PhamKinzo Matsumoto
Dec 29, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Garima SharmaHyoung-Chun Kim

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