The nNOS-p38MAPK Pathway Is Mediated by NOS1AP during Neuronal Death

Li, Lili; Ginet, Vanessa; Liu, Xiaonan; Vergun, O; Tuittila, Minna; Mathieu, Marc; Bonny, Christophe; Puyal, Julien; Truttmann, Anita C.; Courtney, Michael J.

doi:10.1523/jneurosci.4578-12.2013

Cited by 82 publications

(132 citation statements)

References 68 publications

Supporting

Mentioning

121

Contrasting

Unclassified

Order By: Relevance

“…The activated ASK1 itself activates promitogen activated protein kinase kinase MEKK3/6, MKK4/7, and JNK by a phosphorylation cascade. The activated JNK promotes the release of cytochrome C and the formation of an apoptosome, thus leading to apoptosis (Li et al, 2013;Arshad et al, 2013). Moreover, dual-luciferase report and Western blot assays showed that miR-21 obviously reduced the expression of FASLG.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-21 promotes proliferation of rat hepatocyte BRL-3A by targeting FASLG

Li¹,

Chan²,

Leung³

et al. 2015

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. Rat liver regeneration (RLR) induced by partial hepatectomy involves cell proliferation regulated by numerous factors, including microRNAs (miRNAs). miRNA high-throughput sequencing has been established and used to analyze miRNA expression profiles. This study showed that 39 miRNAs were related to RLR through the analysis of miRNA high-throughput sequencing. Their role toward rat normal hepatocyte line BRL-3A was studied by gain-and lossof-function analyses, and one of them, microRNA-21 (miR-21), obviously upregulated and promoted BRL-3A cell proliferation. Using bioinformatics to search for miR-21 targets revealed that Fas ligand (FASLG) is one of miR-21's target genes. A dual-luciferase report assay and Western blot assay showed that miR-21 directly targeted the 3'-untranslated region of FASLG and inhibited the expression of FASLG, which suggests that miR-21 promoted BRL-3A cell proliferation by reducing FASLG expression.

show abstract

Section: Discussionmentioning

confidence: 99%

MicroRNA-21 promotes proliferation of rat hepatocyte BRL-3A by targeting FASLG

Li¹,

Chan²,

Leung³

et al. 2015

Genet. Mol. Res.

View full text Add to dashboard Cite

show abstract

“…Accumulating evidence has demonstrated that recruitment of the Ca 2? -dependent enzyme nNOS via PSD95 is a key contributor to neuronal dysfunction [19][20][21][22][23][24]. Our result showed that interaction of APPL1 with PSD95 through the PDZ2 domain results in activation of the neuroprotective Akt pathway.…”

Section: Appl1 S707a Disrupts Synaptic Activity-mediated Activation Omentioning

confidence: 88%

Serine 707 of APPL1 is Critical for the Synaptic NMDA Receptor-Mediated Akt Phosphorylation Signaling Pathway

Wang

Chen

et al. 2016

Neurosci. Bull.

View full text Add to dashboard Cite

Accumulating evidence indicates that the synaptic activation of N-methyl-D-aspartate receptors (NMDARs) has a neuroprotective effect on neurons. Our previous study demonstrated that APPL1 (adaptor protein containing pleckstrin homology domain, phosphotyrosinebinding domain, and leucine zipper motif) mediates the synaptic activity-dependent activation of PI3K-Akt signaling via coupling this pathway with NMDAR-PSD95 (postsynaptic density protein 95) complexes. However, the molecular mechanism underlying this process is still unknown. In the present study, we investigated the interaction of APPL1 with PSD95 using co-immunocytochemical staining and western blotting. We found that the PDZ2 domain of PSD95 is a binding partner of APPL1. Furthermore, we identified serine 707 of APPL1, a predicted phosphorylation site within the PDZ-binding motif at the C-terminus, as critical for the binding of APPL1 to PSD95, as well as for activation of the Akt signaling pathway during synaptic activity. This suggests that serine 707 of APPL1 is a potential phosphorylation site and may be involved in regulating the neuroprotective Akt signaling pathway that depends on synaptic NMDAR activity.

show abstract

“…It was reported that the nNOS-p38MAPK pathway is mediated by CAPON during neuronal death after an excitotoxic stimulus. 27 L-TAT-GESV, a cell-permeable peptide, can compete for the unique PdZ domain of nNOS that interacts with CAPON and can double the amount of survival tissue in a severe model of neonatal hypoxia-ischemia. CAPON may be a new high-specificity target for ischemia.…”

Section: Downstream Molecules Of Nnosmentioning

confidence: 99%

“…Cao et al 37 found that NOS inhibitors reduce both glutamate-induced p38 activation and the resulting neuronal death. Li et al 27 reported that excitotoxic activation of p38MAPK and subsequent neuronal death were reduced by competition with the nNOS-CAPON interaction and by knockdown with CAPON-targeting small interfering RNAs. nNOS-CAPON uncouplers and p38MAPK inhibitors may become new types of anti-ischemia drugs.…”

Section: Downstream Molecules Of Nnosmentioning

confidence: 99%