Please use this identifier to cite or link to this item:
Title: Substance P protects spiral ganglion neurons from apoptosis via PKC-Ca2+-MAPK/ERK pathways
Authors: Lallemend, F
Lefebvre, PP
Hans, G
RIGO, Jean-Michel 
Van De Water, TR
Moonen, G
Malgrange, B.
Issue Date: 2003
Source: JOURNAL OF NEUROCHEMISTRY, 87(2). p. 508-521
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.
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.
Keywords: apoptosis; neuroprotection; NK1; spiral ganglion neurons; substance P
Document URI:
ISSN: 0022-3042
e-ISSN: 1471-4159
DOI: 10.1046/j.1471-4159.2003.02014.x
ISI #: 000185596100024
Category: A1
Type: Journal Contribution
Appears in Collections:Research publications

Show full item record


checked on Sep 2, 2020


checked on May 13, 2022

Page view(s)

checked on May 17, 2022

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.