PACAP and NGF cooperatively enhance choline acetyltransferase activity in postnatal basal forebrain neurons by complementary induction of its different mRNA species

Yuhara, Aki; Ishii, Kyoko; Nishio, Chika; Abiru, Yasuhiro; Yamada, Masashi; Nawa, Hiroyuki; Hatanaka, Hiroshi; Takei, Nobuyuki

doi:10.1016/s0006-291x(02)03037-1

Cited by 12 publications

(11 citation statements)

References 32 publications

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“…LIF is known to act as a cholinergic differentiation factor (Murphy et al 1997), for instance mediating the phenotypic switch from catecholaminergic to cholinergic for sympathetic neurons (Bamber et al 1994) and upregulating ChAT activity in spinal cord neurons (Michikawa et al 1992). PACAP is thought to mediate the formation of the cholinergic phenotype of rat forebrain neurons and enhances ChAT activity in these cells (Takei et al 2000;Yuhara et al 2003). It does not appear from our results that either LIF or PACAP, or their combination, can induce the complete switch of SH-SY5Y cells to a cholinergic phenotype.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…Recent findings suggest that NGF and PACAP can act additively or cooperatively to regulate cellular processes, including gene expression (Hashimoto et al, 2000;Sakai et al, 2001;Grumolato et al, 2003;Yuhara et al, 2003). Because PACAP, like NGF, also activates PNMT promoter-driven gene transcription , the combined effect of NGF and PACAP on PNMT promoter activity was examined in PC-12 cells transfected with the pGL3RP893 construct (Fig.…”

Section: Ngf and Adrenergic Function 1795mentioning

confidence: 99%

“…Recent studies have shown that PACAP complements the actions of NGF in chromaffin cell development (Grumolato et al, 2003), forebrain cholinergic neuronal survival (Yuhara et al, 2003), PC-12 and hippocampal neuronal survival , and neuritogenesis (DiCicco-Bloom et al, 2000;Sakai et al, 2004), effects probably orchestrated through gene expression. NGF and PACAP have also been shown to cooperatively activate several genes, including the choline acetyltransferase gene (Yuhara et al, 2003) and the PACAP gene itself (Hashimoto et al, 2000;Sakai et al, 2001). Findings de-NGF and Adrenergic Function scribed in this report now demonstrate that NGF and PACAP synergistically activate yet another gene, the PNMT gene.…”

mentioning

confidence: 99%

Nerve Growth Factor Regulates Adrenergic Expression

Tai

Wong-Faull²,

Claycomb³

et al. 2006

Molecular Pharmacology

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The mechanism by which nerve growth factor (NGF) regulates adrenergic expression was examined in PC-12 cells transfected with a rat phenylethanolamine N-methyl-transferase (PNMT) promoter-luciferase reporter gene construct pGL3RP893. NGF treatment increased PNMT promoter-driven luciferase activity in a dose-and time-dependent manner. Induction was attenuated by inhibition of the extracellular signalregulated kinase mitogen-activated protein kinase (MAPK) pathway (ϳ60%) but not by inhibition of the protein kinase A (PKA), protein kinase C, phosphoinositol kinase, or p38 MAPK pathways. Deletion PNMT promoter-luciferase reporter gene constructs showed that the NGF-responsive sequences lay within the proximal Ϫ392 base pairs (bp) of PNMT promoter, wherein binding elements for Egr-1 (Ϫ165 bp) and Sp1 (Ϫ48 bp) reside. Western analysis further showed that NGF increased nuclear levels of Egr-1, but not Sp1 or the catalytic subunit of PKA. Gel mobility shift assays showed increased potential for Egr-1, but not Sp1, protein-DNA binding complex formation. Mutation of either the Egr-1 or Sp1 binding sites in the PNMT promoter attenuated NGF activation. NGF, combined with pituitary adenylyl cyclase-activating protein (PACAP), another PNMT transcriptional activator, cooperatively stimulated PNMT promoter driven-luciferase activity beyond levels observed with either neurotrophin alone. Finally, posttranscriptional control seems to be another important mechanism by which neurotrophins regulate the adrenergic phenotype. NGF, PACAP, and a combination of the two stimulated both intron-retaining and intronless PNMT mRNA and PNMT protein, but to different extents.

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“…It is based on the presynaptic deficits found in the brains of patients and studies of the role of Ach in animal and human behavior. Previous studies revealed that PACAP cooperating with nerve growth factor (NGF) maintained cholinergic function through increasing choline acetyltransferase (ChAT) activity [35][36][37]. However, this hypothesis is not widely supported because the drugs based on it have not been very effective.…”

Section: Pacap and Alzheimer's Diseasementioning

confidence: 99%

Therapeutic potential of PACAP for neurodegenerative diseases

Yang

Jiang

et al. 2015

Cellular and Molecular Biology Letters

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Pituitary adenylate cyclase activating polypeptide (PACAP) is widely expressed in the central and peripheral nervous system. PACAP can initiate multiple signaling pathways through binding with three class B G-protein coupled receptors, PAC1, VPAC1 and VPAC2. Previous studies have revealed numerous biological activities of PACAP in the nervous system. PACAP acts as a neurotransmitter, neuromodulator and neurotrophic factor. Recently, its neuroprotective potential has been demonstrated in numerous in vitro and in vivo studies. Furthermore, evidence suggests that PACAP might move across the blood-brain barrier in amounts sufficient to affect the brain functions. Therefore, PACAP has been examined as a potential therapeutic method for neurodegenerative diseases. The present review summarizes the recent findings with special focus on the models of Alzheimer's disease (AD) and Parkinson's disease (PD). Based on these observations, the administered PACAP inhibits pathological processes in models of AD and PD, and alleviates clinical symptoms. It thus offers a novel therapeutic approach for the treatment of AD and PD.

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PACAP and NGF cooperatively enhance choline acetyltransferase activity in postnatal basal forebrain neurons by complementary induction of its different mRNA species

Cited by 12 publications

References 32 publications

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

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

Nerve Growth Factor Regulates Adrenergic Expression

Therapeutic potential of PACAP for neurodegenerative diseases

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