Angiotensin II Blocks Nicotine-Mediated Neuroprotection against β-Amyloid (1-42) via Activation of the Tyrosine Phosphatase SHP-1

Seán Shaw, Merouane Bencherif, Mario B Marrero

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

We showed recently that nicotine activates the growth-promoting enzyme Janus kinase 2 (JAK2) in PC12 cells and that preincubation of these cells with the JAK2-specific inhibitor AG-490 blocked the nicotine-induced neuroprotection against β-amyloid (1-42) [Aβ (1-42)]. These results provided direct evidence for linkage between JAK2 and the α7 nicotinic acetylcholine receptor-induced neuroprotection in PC12 cells. We also showed that preincubation with angiotensin II (Ang II), functioning via the angiotensin II type 2 (AT2) receptor, blocked both the nicotine-induced activation of JAK2 and its neuroprotection against Aβ (1-42). Recently growth-inhibitory effects of the AT2 receptor have been reported to be mediated by the activation of protein tyrosine phosphatases (PTPases) and that AT2 receptor stimulation is associated with a rapid activation of the PTPase SHP-1 (the cytoplasmic tyrosine phosphatase that contains Src homology 2 domains), a negative regulator of JAK2 signaling. Therefore, the potential biological significance of AT2 receptor-induced effects on both the nicotine-induced activation of JAK2 and its neuroprotection against Aβ (1-42) led us to investigate whether SHP-1 activation could be involved in this process. We found that Ang II induced the activation of SHP-1 and that an antisense against SHP-1 not only augmented the nicotine-induced tyrosine phosphorylation of JAK2 but also blocked the Ang II neutralization of the nicotine-induced neuroprotection. These results demonstrate that nicotine-induced tyrosine phosphorylation of JAK2 and neuroprotection against Aβ (1-42) in PC12 cells are blocked by Ang II via AT2 receptor-induced activation of SHP-1.

Original languageEnglish (US)
Pages (from-to)11224-11228
Number of pages5
JournalJournal of Neuroscience
Volume23
Issue number35
StatePublished - Dec 3 2003

Fingerprint

Non-Receptor Type 6 Protein Tyrosine Phosphatase
Janus Kinase 2
Nicotine
Amyloid
Angiotensin II
Angiotensin Type 2 Receptor
PC12 Cells
Protein Tyrosine Phosphatases
Tyrosine
Phosphorylation
src Homology Domains
Neuroprotection
Nicotinic Receptors
Growth

Keywords

  • Alzheimer's disease
  • Ang II
  • JAK2
  • Neuroprotection
  • Nicotine
  • PC12 cells
  • Phosphatydylinositol-3-kinase
  • SHP-1

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Angiotensin II Blocks Nicotine-Mediated Neuroprotection against β-Amyloid (1-42) via Activation of the Tyrosine Phosphatase SHP-1. / Shaw, Seán; Bencherif, Merouane; Marrero, Mario B.

In: Journal of Neuroscience, Vol. 23, No. 35, 03.12.2003, p. 11224-11228.

Research output: Contribution to journalArticle

Shaw, Seán ; Bencherif, Merouane ; Marrero, Mario B. / Angiotensin II Blocks Nicotine-Mediated Neuroprotection against β-Amyloid (1-42) via Activation of the Tyrosine Phosphatase SHP-1. In: Journal of Neuroscience. 2003 ; Vol. 23, No. 35. pp. 11224-11228.
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