The Neuropeptide Pituitary Adenylate Cyclase‐Activating Polypeptide Exerts Anti‐Apoptotic and Differentiating Effects during Neurogenesis: Focus on Cerebellar Granule Neurones and Embryonic Stem Cells

Falluel-Morel, A.; CHAFAI, M.; Vaudry, David; Basille, Magali; Cazillis, Michèle; Aubert, Nicolas; Louiset, Estelle; DeJouffrey, S.; Bigot, J. M.; Fournier, Alain; Gressèns, Pierre; Rostène, William; Vaudry, Hubert; Gonzalez, Bruno J.

doi:10.1111/j.1365-2826.2007.01537.x

Cited by 37 publications

(26 citation statements)

References 64 publications

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“…The effects of PACAP on apoptosis have been well studied on neuronal cells such as cerebellar granule cells, PC12 cells, cortical neurons, and in vivo retinal tissue (Delcourt et al 2007;Falluel-Morel et al 2007;Racz et al 2006Racz et al , 2007aRavni et al 2006;Somogyvari-Vigh and Reglodi 2004). However, several studies indicate that PACAP exerts anti-apoptotic effects also in nonneuronal cells.…”

Section: Discussionmentioning

confidence: 97%

PACAP Has Anti-apoptotic Effect in the Salivary Gland of an Invertebrate Species, Helix pomatia

et al. 2008

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Pituitary adenylate cyclase activating polypeptide (PACAP) shows a remarkable sequence similarity among species and several studies provide evidence that the functions of PACAP have also been conserved among vertebrate species. Relatively little is known about its presence and functions in invertebrates. The aim of the present study was to investigate whether the well-known anti-apoptotic effect of PACAP can also be demonstrated in invertebrates. This effect was studied in the salivary gland of a molluscan species, Helix pomatia. In this work, we first showed the presence of PACAP-like immunoreactivity in the Helix salivary gland by means of immunohistochemistry. Radioimmunoassay measurements showed that PACAP38-like immunoreactivity dominated in the salivary gland of both active and inactive snails and its concentration was higher in active than in inactive animals in contrast to PACAP27-like immunoreactivity, which did not show activity-dependent changes. PACAP induced a significant elevation of cAMP level in salivary gland extracts. Application of apoptosis-inducing agents, dopamine and colchicine, led to a marked increase in the number of terminal uridine deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells in the salivary gland, which was significantly attenuated by PACAP treatment. In a similar manner, the number of caspase-positive cells was reduced after co-application of dopamine and PACAP. Taken together, the data indicate that PACAP activates cAMP in a molluscan species and we show, for the first time, that PACAP is anti-apoptotic in the invertebrate Helix pomatia.

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Section: Discussionmentioning

confidence: 97%

PACAP Has Anti-apoptotic Effect in the Salivary Gland of an Invertebrate Species, Helix pomatia

et al. 2008

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“…The neuroprotective and neurotrophic actions of PACAP were first reported by Arimura et al (1994), and subsequent work from his lab has revealed much about the mechanisms that are involved (Li et al 2005). There is now great interest in PACAP as a possible differentiation factor for embryonic stem (ES) cells that could be used to induce a neuronal phenotype (Cazillis et al 2004;Falluel-Morel et al 2007). LIF is particularly known for its ability to suppress the differentiation of mouse ES cells in culture (Smith et al 1988;Williams et al 1988) but was ineffective for human ES cells, which appear to require different signals to maintain them in a pluripotent state (Dahéron et al 2004;Okita and Yamanaka 2006).…”

Section: Introductionmentioning

confidence: 98%

Neurotrophic Actions of PACAP-38 and LIF on Human Neuroblastoma SH-SY5Y Cells

Monaghan¹,

Pou²,

Mackenzie³

et al. 2008

J Mol Neurosci

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The neurotrophic actions of pituitary adenylate cyclase-activating polypeptide (PACAP)-38 and leukemia inhibitory factor (LIF) were investigated in human neuroblastoma SH-SY5Y cells. Effects on differentiation were assessed through monitoring morphological changes and Western blot analysis of the expression of neuronal marker proteins. In contrast to PACAP-38, which induced a 5.5-fold increase in the number of neurite-bearing cells, LIF had no significant effect on cell morphology compared to control cells over the 4-day time course. Cells co-treated with PACAP-38+LIF showed a similar increase in neurite-bearing cells compared to those treated with PACAP-38 alone. Cell morphology was similar for PACAP-38-treated and PACAP-38+LIF-co-treated cells, with the formation of bipolar neuron-like cells with long thin neurites, topped by growth cone-like structures and varicosities. SH-SY5Y cells express tyrosine hydroxylase (TH) but only low levels of the neuronal marker proteins: Bcl-2, GAP-43 and choline acetyltransferase (ChAT). Treatment of cells with PACAP-38 induced the expression of Bcl-2, GAP-43, and ChAT but did not appear to alter the expression of TH. LIF failed to induce the expression of GAP-43 and had little effect on the expression of TH, but did induce the expression of Bcl-2 and upregulated the expression of ChAT. Co-treatment with LIF had no effect on PACAP-38-induced expression of Bcl-2, GAP-43, and ChAT. Cells differentiated for 4 days with PACAP-38 or treated with LIF also displayed increased resistance to hypoxic conditions and to treatment with H2O2 and TNFalpha. The increased resistance to hypoxic conditions for PACAP-differentiated cells was blocked by the p38 MAP kinase inhibitor, SB203580, but not by the MEK1 inhibitor, PD98059. Additionally, cell proliferation assays show that LIF, but not PACAP-38, stimulates proliferation of SH-SY5Y cells, and this observed increase by LIF is not attenuated by co-treatment with PACAP. Further investigation of the intracellular signaling pathways mediating the neurotrophic effects of PACAP on SH-SY5Y cells indicate that neither phospholipase C activation nor Ca2+/calmodulin-dependent kinase II (CAMKII) are involved.

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“…Pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the growing family of neurotrophic and neuroprotective factors playing important roles during neuronal development and protection against different types of injuries, like cerebellar and cortical development, protection against Parkinson's disease, excitotoxicity, and ischemia (Waschek 2002;Somogyvari-Vigh and Reglodi 2004;Shioda et al 2006;Falluel-Morel et al 2007). PACAP and its receptors are present in the eye (Seki et al 2000a, b;Vereczki et al 2006), and various different effects on inflammatory processes, cytokine production, vascular supply, and circadian functions have already been demonstrated (Nilsson 1994;Jozsa et al 2001;Hannibal and Fahrenkrug 2004;Nakatani et al 2006).…”

Section: Introductionmentioning

confidence: 99%

PACAP-Mediated Neuroprotection of Neurochemically Identified Cell Types in MSG-Induced Retinal Degeneration

et al. 2008

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Pituitary adenylate cyclase-activating polypeptide (PACAP) is neuroprotective in animal models of different brain pathologies and injuries, including cerebral ischemia, Parkinson's disease, and different types of retinal degenerations. We have previously shown that PACAP is protective against monosodium glutamate (MSG)-induced retinal degeneration, where PACAP-treated retinas has more retained structure and PACAP induces anti-apoptotic while it inhibits pro-apoptotic signaling pathways. The aim of the present study was to investigate cell-type specific effects of PACAP in MSG-induced retinal degeneration by means of immunohistochemistry. Rat pups received MSG (2 mg/g b.w.) applied on postnatal days 1, 5, and 9. PACAP (100 pmol in 5 microl saline) was injected into the right vitreous body, while the left eye received only saline. Retinas were processed for immunocytochemistry after 3 weeks. Immunolabeling was determined for vesicular glutamate transporter 1, tyrosine hydroxylase, calretinin, calbindin, parvalbumin, and vesicular gamma-aminobutyric acid (GABA) transporter. In the MSG-treated retinas, the cell bodies and processes in the inner nuclear, inner plexiform, and ganglion cell layers displayed less immunoreactivity for all antisera. Apart from photoreceptors, only one major retinal cell type examined in this study; the calbindin-immunoreactive horizontal cell seemed not to be affected by MSG application. After simultaneous application of MSG and PACAP, staining of retinas was similar to that of normal eyes, with no significant alterations in immunoreactive patterns. These findings further support the neuroprotective function of PACAP in MSG-induced retinal degeneration.

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The Neuropeptide Pituitary Adenylate Cyclase‐Activating Polypeptide Exerts Anti‐Apoptotic and Differentiating Effects during Neurogenesis: Focus on Cerebellar Granule Neurones and Embryonic Stem Cells

Cited by 37 publications

References 64 publications

PACAP Has Anti-apoptotic Effect in the Salivary Gland of an Invertebrate Species, Helix pomatia

PACAP Has Anti-apoptotic Effect in the Salivary Gland of an Invertebrate Species, Helix pomatia

Neurotrophic Actions of PACAP-38 and LIF on Human Neuroblastoma SH-SY5Y Cells

PACAP-Mediated Neuroprotection of Neurochemically Identified Cell Types in MSG-Induced Retinal Degeneration

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