Attenuation by PACAP of glutamate-induced neurotoxicity in cultured retinal neurons

Shoge, Keisuke; Mishima, Hiromu K.; Saitoh, Tomoya; Ishihara, Kumatoshi; Tsutsumi, Yutaka; Shiomi, Hirohito; Sasa, Masashi

doi:10.1016/s0006-8993(99)01690-x

Cited by 72 publications

(59 citation statements)

References 30 publications

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“…PACAP peptides exhibit neurotrophic effects on developing neurons; activation of PAC1 receptors by PACAP promotes precursor mitosis, neuronal survival, neurite outgrowth and differentiation, and neurotransmission (Waschek, 2002). In addition to its role during development, PACAP exhibits protective effects on neuronal death (Shoge et al, 1999;Silveira et al, 2002). During Xenopus development, PACAP and its PAC1 receptors are expressed in the brain and spinal cord; shortly after neural tube closure, PACAP mRNA was detected dorsolaterally, whereas PAC1 mRNA was localized ventrally in the anterior spinal cord (Hu et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Direct cAMP Signaling through G-Protein-Coupled Receptors Mediates Growth Cone Attraction Induced by Pituitary Adenylate Cyclase-Activating Polypeptide

et al. 2003

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Developing axons are guided to their appropriate targets by environmental cues through the activation of specific receptors and intracellular signaling pathways. Here we report that gradients of pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide widely expressed in the developing nervous system, induce marked attraction of Xenopus growth cones in vitro. PACAP exerted its chemoattractive effects through PAC1, a PACAP-selective G-protein-coupled receptor (GPRC) expressed at the growth cone. Furthermore, the attraction depended on localized cAMP signaling because it was completely blocked either by global elevation of intracellular cAMP levels using forskolin or by inhibition of protein kinase A using specific inhibitors. Moreover, local direct elevation of intracellular cAMP by focal photolysis of caged cAMP compounds was sufficient to induce growth cone attraction. On the other hand, blockade of Ca 2ϩ , phospholipase C, or phosphatidyl inositol-3 kinase signaling pathways did not affect PACAP-induced growth cone attraction. Finally, PACAP-induced attraction also involved the Rho family of small GTPases and required local protein synthesis. Taken together, our results establish cAMP signaling as an independent pathway capable of mediating growth cone attraction induced by a physiologically relevant peptide acting through GPCRs. Such a direct cAMP pathway could potentially operate in other guidance systems for the accurate wiring of the nervous system.

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Section: Discussionmentioning

confidence: 99%

Direct cAMP Signaling through G-Protein-Coupled Receptors Mediates Growth Cone Attraction Induced by Pituitary Adenylate Cyclase-Activating Polypeptide

et al. 2003

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“…The fi rst in vitro studies presented that VIP, a related peptide to PACAP [ 48 ], or PACAP1-27 and PACAP1-38 [ 49 ] have retinoprotective effect against glutamate toxicity using cultured retinal neurons. PACAP1-27, PACAP1-38, and VIP increased [ 40 ] found that anisomycin (1 μg/ml) inhibited protein synthesis and induced cell death in the neuroblastic layer of retinal explants from newborn rats.…”

Section: In Vitro Protective Effects In the Neural Retinamentioning

confidence: 99%

Protective Effects of PACAP in the Retina

Atlasz

Vaczy

Werling

et al. 2016

Current Topics in Neurotoxicity

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Pituitary adenylate cyclase activating polypeptide (PACAP) is a widespread neuropeptide that is well known for its general cytoprotective effects in different neuronal injuries, such as traumatic brain and spinal cord injury, models of neurodegenerative diseases, and cerebral ischemia. PACAP and its receptors also occur in the retina. In this review, we summarize the retinoprotective effects of PACAP. In vitro, PACAP is protective against glutamate, thapsigargin, anisomycin, oxidative stress, UV light, high glucose, infl ammation, and anoxia. Both the neural retina and the pigment epithelial cells can be protected by PACAP in various experimental paradigms. In vivo, the protective effects of intravitreal PACAP treatment have been shown in the following models in rats and mice: excitotoxic injury induced by glutamate, N -methyl-D -aspartate (NMDA) or kainate, ischemic injury induced by carotid artery ligation and high intraocular pressure, degeneration caused by UV-A light, optic nerve transection, and streptozotocin-induced diabetic retinopathy as well as retinopathy of prematurity. Molecular biological methods have revealed that PACAP activates anti-apoptotic, while inhibits pro-apoptotic signaling pathways, and it also stimulates an anti-infl ammatory environment in the retina. Altogether, PACAP is suggested to be a potential therapeutic retinoprotective agent in various retinal diseases.

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“…PACAP can also directly protect cultured cortical neurons from the cytotoxic effects of high concentrations of glutamate (Morio et al, 1996). A neuroprotective effect of PACAP on glutamate-induced neurotoxicity also has been reported in cultured retinal neurons (Shoge et al, 1999). Most of the actions of PACAP on cortical neurons are mediated through the cAMP pathway (Martin et al, 1995;Morio et al, 1996) although it has been reported that PACAP can directly modulate N-methyl-D-aspartate receptors independently of intracellular second messengers (Liu and Madsen, 1997).…”

Section: Pituitary Adenylate Cyclase Activating Peptide (Pacap)mentioning

confidence: 99%

Class II G Protein-Coupled Receptors and Their Ligands in Neuronal Function and Protection

Martin

Maturana²,

Brenneman

et al. 2005

NMM

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G protein-coupled receptors (GPCRs) play pivotal roles in regulating the function and plasticity of neuronal circuits in the nervous system. Among the myriad of GPCRs expressed in neural cells, class II GPCRs which couples predominantly to the Gs-adenylate cyclase-cAMP signaling pathway, have recently received considerable attention for their involvement in regulating neuronal survival. Neuropeptides that activate class II GPCRs include secretin, glucagon-like peptides (GLP-1 and GLP-2), growth hormone-releasing hormone (GHRH), pituitary adenylate cyclase activating peptide (PACAP), corticotropin-releasing hormone (CRH), vasoactive intestinal peptide (VIP), parathyroid hormone (PTH), and calcitonin-related peptides. Studies of patients and animal and cell culture models, have revealed possible roles for class II GPCRs signaling in the pathogenesis of several prominent neurodegenerative conditions including stroke, Alzheimer's, Parkinson's, and Huntington's diseases. Many of the peptides that activate class II GPCRs promote neuron survival by increasing the resistance of the cells to oxidative, metabolic, and excitotoxic injury. A better understanding of the cellular and molecular mechanisms by which class II GPCRs signaling modulates neuronal survival and plasticity will likely lead to novel therapeutic interventions for neurodegenerative disorders.

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Attenuation by PACAP of glutamate-induced neurotoxicity in cultured retinal neurons

Cited by 72 publications

References 30 publications

Direct cAMP Signaling through G-Protein-Coupled Receptors Mediates Growth Cone Attraction Induced by Pituitary Adenylate Cyclase-Activating Polypeptide

Direct cAMP Signaling through G-Protein-Coupled Receptors Mediates Growth Cone Attraction Induced by Pituitary Adenylate Cyclase-Activating Polypeptide

Protective Effects of PACAP in the Retina

Class II G Protein-Coupled Receptors and Their Ligands in Neuronal Function and Protection

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