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http://hdl.handle.net/1942/9434
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DC Field | Value | Language |
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dc.contributor.author | Lallemend, F | - |
dc.contributor.author | Lefebvre, PP | - |
dc.contributor.author | Hans, G | - |
dc.contributor.author | RIGO, Jean-Michel | - |
dc.contributor.author | Van De Water, TR | - |
dc.contributor.author | Moonen, G | - |
dc.contributor.author | Malgrange, B. | - |
dc.date.accessioned | 2009-04-08T12:53:59Z | - |
dc.date.issued | 2003 | - |
dc.identifier.citation | JOURNAL OF NEUROCHEMISTRY, 87(2). p. 508-521 | - |
dc.identifier.issn | 0022-3042 | - |
dc.identifier.uri | http://hdl.handle.net/1942/9434 | - |
dc.description.abstract | In the current study, we have investigated the ability of substance P (SP) to protect 3-day-old (P3) rat spiral ganglion neurons (SGNs) from trophic factor deprivation (TFD)-induced cell death. The presence of SP high affinity neurokinin-1 receptor (NK1) transcripts was detected in the spiral ganglion and the NK1 protein localized to SGNs both ex vivo and in vitro. Treatment with SP increased cytoplasmic Ca2+ in SGNs, further arguing for the presence of functional NK1 on these neurons. Both SP and the agonist [Sar(9), Met(O-2)(11)]-SP significantly decreased SGN cell death induced by TFD, with no effect on neurite outgrowth. The survival promoting effect of SP was blocked by the NK1 antagonist, WIN51708. Both pan-caspase inhibitor BOC-D-FMK and SP treatments markedly reduced activation of caspases and DNA fragmentation in trophic factor deprived-neurons. The neuroprotective action of SP was antagonised by specific inhibitors of second messengers, including 1.2-bis-(O-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM) to chelate cytosolic Ca2+, the protein kinase C (PKC) inhibitors bisindolylmaleimide I, Go6976 and LY333531 and the MAPK/ERK inhibitor U0126. In contrast, nifedipine, a specific inhibitor of L-type Ca2+ channel, and LY294002, a phosphatidylinositol-3-OH kinase (PI3K) inhibitor, had no effect on SP trophic support of SGNs. Moreover, activation of endogenous PKC by 4beta-phorbol 12-myristate 13-acetate (PMA) also reduced the loss of trophic factor-deprived SGNs. Thus, NK1 expressed by SGNs transmit a survival-promoting regulatory signal during TFD-induced SGN cell death via pathways involving PKC activation, Ca2+ signalling and MAPK/ERK activation, which can be accounted for by an inhibition of caspase activation. | - |
dc.language.iso | en | - |
dc.publisher | BLACKWELL PUBLISHING LTD | - |
dc.subject.other | apoptosis; neuroprotection; NK1; spiral ganglion neurons; substance P | - |
dc.title | Substance P protects spiral ganglion neurons from apoptosis via PKC-Ca2+-MAPK/ERK pathways | - |
dc.type | Journal Contribution | - |
dc.identifier.epage | 521 | - |
dc.identifier.issue | 2 | - |
dc.identifier.spage | 508 | - |
dc.identifier.volume | 87 | - |
local.bibliographicCitation.jcat | A1 | - |
dc.description.notes | Univ Liege, Res Ctr Cellular & Mol Neurobiol, Liege, Belgium. Univ Liege, Dept Otorhinolaryngol, Liege, Belgium. Univ Liege, Dept Neurol, Liege, Belgium. Univ Miami, Sch Med, Dept Otolaryngol, Miami, FL USA. | - |
local.type.refereed | Refereed | - |
local.type.specified | Review | - |
dc.bibliographicCitation.oldjcat | A1 | - |
dc.identifier.doi | 10.1046/j.1471-4159.2003.02014.x | - |
dc.identifier.isi | 000185596100024 | - |
item.fulltext | No Fulltext | - |
item.fullcitation | Lallemend, F; Lefebvre, PP; Hans, G; RIGO, Jean-Michel; Van De Water, TR; Moonen, G & Malgrange, B. (2003) Substance P protects spiral ganglion neurons from apoptosis via PKC-Ca2+-MAPK/ERK pathways. In: JOURNAL OF NEUROCHEMISTRY, 87(2). p. 508-521. | - |
item.contributor | Lallemend, F | - |
item.contributor | Lefebvre, PP | - |
item.contributor | Hans, G | - |
item.contributor | RIGO, Jean-Michel | - |
item.contributor | Van De Water, TR | - |
item.contributor | Moonen, G | - |
item.contributor | Malgrange, B. | - |
item.accessRights | Closed Access | - |
crisitem.journal.issn | 0022-3042 | - |
crisitem.journal.eissn | 1471-4159 | - |
Appears in Collections: | Research publications |
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