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Intracellular nitric oxide mediates the neuroproliferative effect of Neuropeptide Y on postnatal hippocampal precursor cells

Intracellular nitric oxide mediates the neuroproliferative effect of Neuropeptide Y on postnatal hippocampal precursor cells
Intracellular nitric oxide mediates the neuroproliferative effect of Neuropeptide Y on postnatal hippocampal precursor cells
Neuropeptide Y (NPY) is widely expressed in the central and peripheral nervous systems and is proliferative for a range of cells types in vitro. NPY plays a key role in regulating adult hippocampal neurogenesis in vivo under both basal and pathological conditions, although the underlying mechanisms are largely unknown. We have investigated the role of nitric oxide (NO) on the neurogenic effects of NPY. Using postnatal rat hippocampal cultures, we show that the proliferative effect of NPY on nestin-positive precursor cells is NO-dependent. As well as the involvement of neuronal nitric oxide synthase, the proliferative effect is mediated via a NO/cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase (PKG) and extracellular signal-regulated kinase (ERK) 1/2 signalling pathway. We show that NPY-mediated intracellular NO signalling results in an increase in neuroproliferation. By contrast, extracellular NO had an opposite, inhibitory effect, on proliferation. The importance of the NO-cGMP-PKG signalling pathway in ERK 1/2 activation was confirmed using western blotting. This work unites two significant modulators of hippocampal neurogenesis within a common signalling framework and provides a mechanism for the independent extra- and intracellular regulation of postnatal neural precursors by NO.
0021-9258
20187-20196
Cheung, Angela
d3359980-8f16-4aec-9782-373901ec1788
Newland, Philip L
7a018c0e-37ba-40f5-bbf6-49ab0f299dbb
Zaben, Malik
6390c24c-4458-486d-9188-3afda5c91359
Attard, George S
3219075d-2364-4f00-aeb9-1d90f8cd0d36
Gray, William P
dde0eca1-7d39-451d-8914-2cb95f65e025
Cheung, Angela
d3359980-8f16-4aec-9782-373901ec1788
Newland, Philip L
7a018c0e-37ba-40f5-bbf6-49ab0f299dbb
Zaben, Malik
6390c24c-4458-486d-9188-3afda5c91359
Attard, George S
3219075d-2364-4f00-aeb9-1d90f8cd0d36
Gray, William P
dde0eca1-7d39-451d-8914-2cb95f65e025

Cheung, Angela, Newland, Philip L, Zaben, Malik, Attard, George S and Gray, William P (2012) Intracellular nitric oxide mediates the neuroproliferative effect of Neuropeptide Y on postnatal hippocampal precursor cells. The Journal of Biological Chemistry, 287, 20187-20196. (doi:10.1074/jbc.M112.346783). (PMID:22474320)

Record type: Article

Abstract

Neuropeptide Y (NPY) is widely expressed in the central and peripheral nervous systems and is proliferative for a range of cells types in vitro. NPY plays a key role in regulating adult hippocampal neurogenesis in vivo under both basal and pathological conditions, although the underlying mechanisms are largely unknown. We have investigated the role of nitric oxide (NO) on the neurogenic effects of NPY. Using postnatal rat hippocampal cultures, we show that the proliferative effect of NPY on nestin-positive precursor cells is NO-dependent. As well as the involvement of neuronal nitric oxide synthase, the proliferative effect is mediated via a NO/cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase (PKG) and extracellular signal-regulated kinase (ERK) 1/2 signalling pathway. We show that NPY-mediated intracellular NO signalling results in an increase in neuroproliferation. By contrast, extracellular NO had an opposite, inhibitory effect, on proliferation. The importance of the NO-cGMP-PKG signalling pathway in ERK 1/2 activation was confirmed using western blotting. This work unites two significant modulators of hippocampal neurogenesis within a common signalling framework and provides a mechanism for the independent extra- and intracellular regulation of postnatal neural precursors by NO.

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Published date: June 2012
Organisations: Chemistry, Faculty of Medicine, Centre for Biological Sciences

Identifiers

Local EPrints ID: 339757
URI: https://eprints.soton.ac.uk/id/eprint/339757
ISSN: 0021-9258
PURE UUID: a0c943b4-a508-4f0c-86aa-3276731f97f1
ORCID for Philip L Newland: ORCID iD orcid.org/0000-0003-4124-8507
ORCID for George S Attard: ORCID iD orcid.org/0000-0001-8304-0742

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Date deposited: 30 May 2012 09:01
Last modified: 20 Jul 2019 01:21

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