Inhibition of the canonical Wnt signaling pathway by apolipoprotein E4 in PC12 cells

Caruso, Alessandra; Motolese, Marta; Iacovelli, Luisa; Caraci, Filippo; Copani, Agata; Nicoletti, Ferdinando; Terstappen, Georg C.; Gaviraghi, G.; Caricasole, Andrea

doi:10.1111/j.1471-4159.2006.03867.x

Cited by 78 publications

(55 citation statements)

References 58 publications

(59 reference statements)

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“…It has been reported that atRA exerts an antiapoptotic effect in hippocampus cells (Ahlemeyer et al, 2001). In the present study, atRA treatment significantly attenuated CoCl 2 -induced apoptosis of undifferentiated PC12 cells, which has been widely employed as a neuronal cell model by different groups (Caruso et al, 2006;Chen et al, 2008;Misiti et al, 2008). We also found that treatment of undifferentiated PC12 cells with atRA dramatically decreased ROS level and caspase-3 activity, which may account, at least in part, for its antiapoptotic property.…”

Section: Discussionmentioning

confidence: 52%

All‐trans retinoic acid inhibits cobalt chloride‐induced apoptosis in PC12 cells: Role of the dimethylarginine dimethylaminohydrolase/asymmetric dimethylarginine pathway

Wang

Jiang

et al. 2009

J of Neuroscience Research

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Previous studies have shown that the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) and its specific hydrolase dimethylarginine dimethylaminohydrolase (DDAH) are involved in the regulation of apoptosis in different cell types. In the present study, we investigated the role of the DDAH/ADMA pathway in cobalt chloride (CoCl(2))-induced apoptosis and the antiapoptotic effect of all-trans retinoic acid (atRA) in undifferentiated pheochromocytoma (PC12) cells. Treatment of CoCl(2) (125 microM) for 48 hr significantly induced the apoptosis of PC12 cells, concomitantly with increased intracellular reactive oxygen species (ROS) production and caspase-3 activity. CoCl(2) treatment also decreased the activity of DDAH and the expression of DDAH2 (mRNA and protein), resulting in an increased level of ADMA. All these alterations induced by CoCl(2) were attenuated by atRA (0.1, 1, or 10 microM). Interestingly, the antiapoptotic effects of atRA were inhibited by DDAH2 small RNA interference. In contrast, DDAH2 overexpression inhibited the proapoptotic effects of CoCl(2). We also found that treatment of exogenous ADMA (3, 10, or 30 microM) induced the apoptosis of PC12 cells in a concentration- and time-dependent manner, which was inhibited by the antioxidant or the caspase-3 inhibitor. These findings suggest that the modulation of the DDAH/ADMA/ROS pathway plays an important role in CoCl(2)-induced apoptosis and the antiapoptotic effects of atRA in undifferentiated PC12 cells.

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Section: Discussionmentioning

confidence: 52%

All‐trans retinoic acid inhibits cobalt chloride‐induced apoptosis in PC12 cells: Role of the dimethylarginine dimethylaminohydrolase/asymmetric dimethylarginine pathway

Wang

Jiang

et al. 2009

J of Neuroscience Research

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“…Recently, an impairment of Wnt signaling has been proposed as one of the mechanism implicated in the AD pathology, and a relationship between the neuronal effects of b-amyloid protein and the hyperphosphorylation of tau has been strongly suggested [18,34,48]. On the other hand, apolipoprotein Ee4, which is a well-known risk factor for AD, is able to inhibit Wnt signaling [49].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Wnt and PI3K Signaling Modulates GSK-3β Activity and Induces Morphological Changes in Cortical Neurons: Role of Tau Phosphorylation

Mercado-Gómez

Hernández-Fonseca

Villavicencio-Queijeiro

et al. 2008

Neurochem Res

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Glycogen synthase kinase GSK-3beta has been identified as one of the major candidates mediating tau hyperphosphorylation at the same sites as those present in tau protein in brain from Alzheimer's disease (AD) patients. However, the signal transduction pathways involved in the abnormal activation of GSK-3beta, have not been completely elucidated. GSK-3beta activity is repressed by the canonical Wnt signaling pathway, but it is also modulated through the PI3K/Akt route. Recent studies have suggested that Wnt signaling might be involved in the pathophysiology of AD. On the other hand, modulators of the PI3K pathway might be reduced during aging leading to a sustained activation of GSK-3beta, which in turn would increase the risk of tau hyperphosphorylation. The role of Wnt and PI3K signaling inhibition on the extent of tau phosphorylation and neuronal morphology has not been completely elucidated. Thus, in the present investigation we analyzed the effects of different negative modulators of the Wnt and the PI3K pathways on GSK-3beta activation and phosphorylation of tau at the PHF-1 epitope in cortical cultured neurons and hippocampal slices from adult rat brain. Changes in the microtubule network were also studied. We found that a variety of Wnt and PI3K inhibitors, significantly increased tau phosphorylation at the PHF-1 site, induced the disarrangement of the microtubule network and the accumulation of tau within cell bodies. These changes correlated with alterations in neuronal morphology.

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“…Likewise, it was shown that apolipophorins, the ortholog for APOE proteins in Drosophila, copurify and act as vehicles for the movement of lipid-linked morphogens including the Wnt ortholog Wingless (67). Moreover, recent evidence indicates that there may be an isoform-dependent effect of APOE on Wnt signaling activity, where APOE-4 had a strong inhibitory effect on the activity of the signaling cascade (68).…”

Section: Discussionmentioning

confidence: 99%

Common genetic variation within the Low-Density Lipoprotein Receptor-Related Protein 6 and late-onset Alzheimer's disease

Ferrari

Papassotiropoulos

Biechele

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

256

224

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Genome-wide linkage studies have defined a broad susceptibility region for late-onset Alzheimer's disease on chromosome 12, which contains the Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) gene, a coreceptor for Wnt signaling. Here, we report the association between common LRP6 variants and late-onset Alzheimer's disease in a multicenter case-control series as well as in a large family-based series ascertained by the National Institute of Mental Health-National Institute on Aging Genetics Initiative. As shown in the genome-wide linkage studies, our association depends mainly on apolipoprotein E-4 (APOE-4) carrier status. Haplotype tagging single-nucleotide polymorphisms (SNPs) with a set of seven allelic variants of LRP6 identified a putative risk haplotype, which includes a highly conserved coding sequence SNP: Ile-1062 3 Val. Functional analyses revealed that the associated allele Val-1062, an allele previously linked to low bone mass, has decreased ␤-catenin signaling in HEK293T cells. Our study unveils a genetic relationship between LRP6 and APOE and supports the hypothesis that altered Wnt/␤-catenin signaling may be involved in this neurodegenerative disease.neurodegenerative ͉ LRP-6 ͉ single-nucleotide polymorphism ͉ APOE ͉ Wnt

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Inhibition of the canonical Wnt signaling pathway by apolipoprotein E4 in PC12 cells

Cited by 78 publications

References 58 publications

All‐trans retinoic acid inhibits cobalt chloride‐induced apoptosis in PC12 cells: Role of the dimethylarginine dimethylaminohydrolase/asymmetric dimethylarginine pathway

All‐trans retinoic acid inhibits cobalt chloride‐induced apoptosis in PC12 cells: Role of the dimethylarginine dimethylaminohydrolase/asymmetric dimethylarginine pathway

Inhibition of Wnt and PI3K Signaling Modulates GSK-3β Activity and Induces Morphological Changes in Cortical Neurons: Role of Tau Phosphorylation

Common genetic variation within the Low-Density Lipoprotein Receptor-Related Protein 6 and late-onset Alzheimer's disease

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