Opposite regulation of the mitochondrial apoptotic pathway by C2‐ceramide and PACAP through a MAP‐kinase‐dependent mechanism in cerebellar granule cells

Falluel‐Morel, Anthony; Aubert, Nicolas; Vaudry, David; Basille, Magali; Fontaine, Marc; Fournier, Alain; Vaudry, Hubert; Gonzalez, Bruno J.

doi:10.1111/j.1471-4159.2004.02810.x

Cited by 94 publications

(104 citation statements)

References 55 publications

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“…In particular, ceramides have been shown to induce Bax gene expression via JNK-dependent pathway in different cell types. 11,14 Altogether, these results obtained in vitro suggest that apoptosis of cultured granule neurons occurs primarily through activation of the mitochondrial-dependent apoptotic pathway. In addition, the mentioned data may lead to a hypothesis that Bax represents the primary target for both PACAP and ceramides.…”

mentioning

confidence: 68%

“…5 Several processes, such as alterations of expression level and phosphorylation state 20,21 can shift the equilibrium imposed by the Bcl-2 family members. In particular, modifications of their homo/heterodimerization may lead to mitochondrial integrity disruption with release of intermembrane space proteins, such as cytochrome c. 6 Since ceramides and PACAP exert opposite effects on the pro-apoptotic gene Bax expression and, consequently, the protein release from mitochondria, 11,12 we have raised a hypothesis that Bax, as mitochondrial apoptotic pathway activator, has a primary contribution into the apoptotic death of granule neuronal precursors. If so, the repression of Bax gene in these cells should favour their survival in a post-transplantational period.…”

Section: Discussionmentioning

confidence: 99%

“…19 Caspases-3 and -9 were found to be the main targets of PACAP neuroprotective action towards this cell type. 11,12 Several apoptotic pathways have been found to be dependent on different caspases. For example, caspase-8, which can be activated via TNF-a family receptors, is associated with the extrinsic apoptotic pathway.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, it acts as a potent inhibitor of Bax expression when it is induced by ceramides, agents acting as pro-apoptotic factors in these cells. 11 The MAP-kinase pathway appears to be essential for the antiapoptotic effect of PACAP. Besides that, recent data have shown that the PACAP-induced blockade of Bax is mediated by ERK activation.…”

mentioning

confidence: 99%

“…Besides that, recent data have shown that the PACAP-induced blockade of Bax is mediated by ERK activation. 11,12 Ceramides, the metabolites of sphingomyelin, represent important signalling molecules and play crucial roles during neuronal development. 13 They are involved in the regulation of neuronal plasticity, axonogenesis, and cell death.…”

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confidence: 99%

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Bax siRNA promotes survival of cultured and allografted granule cell precursors through blockade of caspase-3 cleavage

et al. 2008

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Transplantation of neuronal precursor cells (NPCs) into the central nervous system could represent a powerful therapeutical tool against neurodegenerative diseases. Unfortunately, numerous NPCs die shortly after transplantation, predominantly due to caspase-dependent apoptosis. Using a culture of cerebellar neuronal precursors, we have previously demonstrated protective effect of the neuropeptide PACAP, which suppresses ceramide-induced apoptosis by blockade of the mitochondrial apoptotic pathway. The main objective of this study was to determine whether Bax repression can promote survival of NPCs allotransplanted into a host animal. In vivo and ex vivo experiments revealed that C2-ceramide increases Bax expression, while PACAP reverses this effect. In vitro tests using cerebellar NPCs demonstrated that the Bax-specific small interfering RNA (siRNA) could reduce their death and caspase-3 cleavage within the first 24 h. BrdU-labelled NPCs were subjected to transfection procedure with or without siRNA introduction before using for in vivo transplantation. Twenty-four hours after, the allografted NPCs containing siRNA showed significantly reduced level of caspase-3 cleavage, and the volume of their implants was almost twofold higher than in the case of empty-transfected precursors. These data evidence an important role of Bax in life/death decision of grafted NPCs and suggest that RNA interference strategy may be applicable for maintaining NPCs survival within the critical first hours after their transplantation.

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confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Bax siRNA promotes survival of cultured and allografted granule cell precursors through blockade of caspase-3 cleavage

et al. 2008

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Neurotrophic Effects of PACAP in the Cerebellar Cortex

Falluel‐Morel

Vaudry

Komuro

et al. 2011

Hormones in Neurodegeneration, Neuroprotection, and Neurogenesis

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Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid peptide that was originally isolated from the ovine hypothalamus on the basis of its ability to stimulate cAMP formation in rat anterior pituitary cells [1]. PACAP belongs to the vasoactive intestinal polypeptide (VIP)-secretin-GHRH-glucagon superfamily. The sequence of PACAP has been remarkably well conserved during evolution, which suggests that the peptide should be involved in the regulation of important biological functions [2]. PACAP acts through three distinct receptors named PAC1-R, VPAC1-R, and VPAC2-R. PACAP has a much higher affinity than VIP for PAC1-R while both peptides bind similarly to VPAC1-R and VPAC2-R. All three receptors are positively coupled to the adenylyl cyclase, but PAC1-R also stimulates the phospholipase C (PLC) and the extracellular regulated kinase (ERK) pathways [3]. PAC1-R has several variants that result mainly from the alternative splicing of the mRNA regions encoding the first extracellular domain and the third intracellular cytoplasmic loop [4], which are coupled to differential transduction mechanisms. For instance, both the short and hop variants strongly activate the protein kinase A (PKA) and PLC pathways, whereas the hip isoform does not signal through the PLC pathway at all [5]. In addition, the hip/hop form displays an intermediate phenotype with a reduced ability to activate both signal transduction pathways [5].PACAP and its receptors are widely distributed in the brain and peripheral organs, and the peptide has been found to exert pleiotropic effects on hormone secretion, vasodilation, regulation of inflammation, and apoptosis [3]. Besides, increasing evidence indicates that PACAP exerts neurotrophic actions during development and neuroprotective activities in the adult brain. Here, we review the current knowledge regarding the role of PACAP during histogenesis of the cerebellar cortex. Expression of PACAP and its Receptors in the Developing CerebellumIn the brain, the highest concentrations of PACAP are found in the hypothalamus and cerebellum [6]. PACAP is detected in the rat brain as early as embryonic day 14

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Atmospheric plasma‐aided biocidal finishes for nonwoven polypropylene fabrics. I. Synthesis and characterization

Gawish

Matthews

Wafa

et al. 2006

J of Applied Polymer Sci

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Novel biocidal fabrics were synthesized by the graft copolymerization of glycidyl methacrylate (GMA) onto plasma-treated nonwoven polypropylene (PP) to produce PP/ GMA grafts. Atmospheric oxygenated helium plasma was used to enhance the PP fabrics' initiation before GMA grafting. The grafted PP/GMA epoxide group was reacted with b-cyclodextrin, monochlorotrizynyl-b-cyclodextrins, or a quaternary ammonium chitosan derivative [N-(2 hydroxy propyl) 3-trimethylammonium chitosan chloride]. Some interesting biocidal agents were complexed into the cyclodextrin (CD) cavity of PP/GMA/CD grafted fabrics. Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and optical and scanning electron microscopies were used to characterize the grafted complexed fabrics. These synthesized biocidal fabrics proved to be antistatic, antimicrobial, and insect-repelling (see part II of this study).

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Opposite regulation of the mitochondrial apoptotic pathway by C2‐ceramide and PACAP through a MAP‐kinase‐dependent mechanism in cerebellar granule cells

Cited by 94 publications

References 55 publications

Bax siRNA promotes survival of cultured and allografted granule cell precursors through blockade of caspase-3 cleavage

Bax siRNA promotes survival of cultured and allografted granule cell precursors through blockade of caspase-3 cleavage

Neurotrophic Effects of PACAP in the Cerebellar Cortex

Atmospheric plasma‐aided biocidal finishes for nonwoven polypropylene fabrics. I. Synthesis and characterization

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