Convergence of alpha 7 nicotinic acetylcholine receptor-activated pathways for anti-apoptosis and anti-inflammation: Central role for JAK2 activation of STAT3 and NF-κB

Mario B Marrero, Merouane Bencherif

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

Our laboratories have previously identified the α7 nAChR-JAK2 pathway as playing a central role in nicotine-induced neuroprotection. We have also reported that the angiotensin II (Ang II) AT2 receptor induced activation of SHP-1 induces the tyrosine dephosphorylation of JAK2 that results in a complete neutralization of the α7 nAChR-JAK2 pro-survival cascade. In this study, we investigated the effects of inhibiting the α7 nAChR-JAK2 pro-survival cascade on the nicotine-induced production of the survival factor Bcl-2 and the transcriptional activation of NF-κB, AP-1, STAT1, STAT3, and STAT5. We report that nicotine induced the production of Bcl-2 and increased the transcriptional activation of NF-κB, AP-1, STAT1, and STAT3, and with the exception of AP-1, the other transcription factors (NF-κB, STAT1, and STAT3) were significantly reduced by JAK2 inhibition. We also demonstrate that, via transfection of either Bcl-2 antisense or NF-κB, STAT1 and STAT3 transcription factor decoys oligodeoxyribonucleotides into PC12 cells, nicotine induces its neuroprotection in PC12 cells via activation of the α7 nAChR-JAK2-(NF-κB; STAT3)-Bcl-2 pro-survival pathway. Finally, the neuroprotective nicotine-induced production of Bcl-2 appears to fully counteract the Aβ (1-42)-induced apoptosis of PC12 cells by blocking Aβ (1-42)-induced mitochondrial release of cytosolic cytochrome C.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalBrain Research
Volume1256
DOIs
StatePublished - Feb 23 2009

Keywords

  • Apoptosis
  • Inflammation
  • Janus kinase
  • NFκB
  • Nicotinic receptor
  • STAT3

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

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