2011年8月
The Akt-Nitric Oxide-cGMP Pathway Contributes to Nerve Growth Factor-Mediated Neurite Outgrowth in Apolipoprotein E Knockout Mice
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
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- 巻
- 338
- 号
- 2
- 開始ページ
- 694
- 終了ページ
- 700
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1124/jpet.111.181487
- 出版者・発行元
- AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
Apolipoprotein E (apo)-deficient [apoE(-/-)] mice have peripheral sensory nerve defects and a reduced and delayed response to noxious thermal stimuli. However, to date, no report has focused on the influence of apoE deficiency on calcitonin gene-related peptide (CGRP)-containing nerve fiber extensions. We have shown that the density of CGRP-containing nerve fibers decreases in mesenteric arteries of apoE(-/-) mice compared with wild-type mice. Here, we investigated whether apoE deficiency is involved in nerve growth factor (NGF)-induced CGRP-containing nerve regeneration using apoE(-/-) mice. NGF-mediated CGRP-like immunoreactivity (LI)-neurite outgrowth in apoE(-/-) cultured dorsal root ganglia (DRG) cells was significantly lower than that in wild-type cultures. However, the level of NGF receptor mRNA in apoE(-/-) DRG cells was similar to that in wild-type mice. To clarify the mechanism of the impaired ability of NGF-mediated neurite outgrowth, we focused on the Akt-nitric oxide (NO)-cGMP pathway. Expression of phosphorylated Akt was significantly reduced in apoE(-/-) DRG. The NO donor, sodium nitroprusside or S-nitroso-N-acetylpenicillamine, did not affect NGF-mediated neurite outgrowth in apoE(-/-) cultured DRG cells. However, 8-bromoguanosine 3',5'-cyclic monophosphate sodium salt n-hydrate, a cGMP analog, induced NGF-mediated nerve facilitation similar to wild-type NGF-mediated neurite outgrowth levels. Furthermore, in apoE(-/-) DRG, soluble guanylate cyclase expression was significantly lower than that in wild-type DRG. These results suggest that in apoE(-/-) mice the Akt-NO-cGMP pathway is impaired, which may be caused by NGF-mediated CGRP-LI-neurite outgrowth defects.
- リンク情報
- ID情報
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- DOI : 10.1124/jpet.111.181487
- ISSN : 0022-3565
- PubMed ID : 21593103
- Web of Science ID : WOS:000292841600030