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- Title
Angiotensin II Blocks Nicotine-Mediated Neuroprotection against Β-Amyloid (1-42) via Activation of the Tyrosine Phosphatase SHP-1.
- Authors
Shaw, Se´n; Bencherif, Merouane; Marrero, Mario B.
- 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 (AT[sub2]) receptor, blocked both the nicotine-induced activation of JAK2 and its neuroprotection against Aβ (1-42). Recently growth-inhibitory effects of the AT[sub2] receptor have been reported to be mediated by the activation of protein tyrosine phosphatases (PTPases) and that AT[sub2] 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 AT[sub2] 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 AT[sub2] receptor-induced activation of SHP-1.
- Subjects
NICOTINE; PROTEIN kinases; CHOLINERGIC receptors; PROTEIN-tyrosine phosphatase; ANTISENSE peptides
- Publication
Journal of Neuroscience, 2003, Vol 23, Issue 35, p11224
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.23-35-11224.2003