Therapeutic concentrations of valproate but not amitriptyline increase neuropeptide Y (NPY) expression in the human SH-SY5Y neuroblastoma cell line

Lorna A. Farrelly, Niall T P Savage, Cristina O'Callaghan, André Toulouse, Deniz M. Yilmazer-Hanke

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Neuropeptide Y (NPY) is a peptide found in the brain and autonomic nervous system, which is associated with anxiety, depression, epilepsy, learning and memory, sleep, obesity and circadian rhythms. NPY has recently gained much attention as an endogenous antiepileptic and antidepressant agent, as drugs with antiepileptic and/or mood-stabilizing properties may exert their action by increasing NPY concentrations, which in turn can reduce anxiety and depression levels, dampen seizures or increase seizure threshold.We have used human neuroblastoma SH-SY5Y cells to investigate the effect of valproate (VPA) and amitriptyline (AMI) on NPY expression at therapeutic plasma concentrations of 0.6. mM and 630. nM, respectively. In addition, 12-O-tetradecanoylphorbol-13-acetate (TPA) known to differentiate SH-SY5Y cells into a neuronal phenotype and to increase NPY expression through activation of protein kinase C (PKC) was applied as a positive control (16. nM). Cell viability after drug treatment was tested with a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. NPY expression was measured using immunofluorescence and quantitative RT-PCR (qRT-PCR). Results from immunocytochemistry have shown NPY levels to be significantly increased following a 72. h but not 24. h VPA treatment. A further increase in expression was observed with simultaneous VPA and TPA treatment, suggesting that the two agents may increase NPY expression through different mechanisms. The increase in NPY mRNA by VPA and TPA was confirmed with qRT-PCR after 72. h. In contrast, AMI had no effect on NPY expression in SH-SY5Y cells.Together, the data point to an elevation of human NPY mRNA and peptide levels by therapeutic concentrations of VPA following chronic treatment. Thus, upregulation of NPY may have an impact in anti-cancer treatment of neuroblastomas with VPA, and antagonizing hypothalamic NPY effects may help to ameliorate VPA-induced weight gain and obesity without interfering with the desired central effects of VPA.

Original languageEnglish
Pages (from-to)123-130
Number of pages8
JournalRegulatory Peptides
Volume186
DOIs
StatePublished - 2013

Fingerprint

Amitriptyline
Neuropeptide Y
Valproic Acid
Neuroblastoma
Cells
Cell Line
Therapeutics
Tetradecanoylphorbol Acetate
Acetates
Anticonvulsants
Seizures
Anxiety
Obesity
Depression
Drug therapy
Polymerase Chain Reaction
Messenger RNA
Peptides
Oncology
Autonomic Nervous System

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

Cite this

Therapeutic concentrations of valproate but not amitriptyline increase neuropeptide Y (NPY) expression in the human SH-SY5Y neuroblastoma cell line. / Farrelly, Lorna A.; Savage, Niall T P; O'Callaghan, Cristina; Toulouse, André; Yilmazer-Hanke, Deniz M.

In: Regulatory Peptides, Vol. 186, 2013, p. 123-130.

Research output: Contribution to journalArticle

Farrelly, Lorna A. ; Savage, Niall T P ; O'Callaghan, Cristina ; Toulouse, André ; Yilmazer-Hanke, Deniz M. / Therapeutic concentrations of valproate but not amitriptyline increase neuropeptide Y (NPY) expression in the human SH-SY5Y neuroblastoma cell line. In: Regulatory Peptides. 2013 ; Vol. 186. pp. 123-130.
@article{af345d07148c42fd9fc360d3d6cec4c6,
title = "Therapeutic concentrations of valproate but not amitriptyline increase neuropeptide Y (NPY) expression in the human SH-SY5Y neuroblastoma cell line",
abstract = "Neuropeptide Y (NPY) is a peptide found in the brain and autonomic nervous system, which is associated with anxiety, depression, epilepsy, learning and memory, sleep, obesity and circadian rhythms. NPY has recently gained much attention as an endogenous antiepileptic and antidepressant agent, as drugs with antiepileptic and/or mood-stabilizing properties may exert their action by increasing NPY concentrations, which in turn can reduce anxiety and depression levels, dampen seizures or increase seizure threshold.We have used human neuroblastoma SH-SY5Y cells to investigate the effect of valproate (VPA) and amitriptyline (AMI) on NPY expression at therapeutic plasma concentrations of 0.6. mM and 630. nM, respectively. In addition, 12-O-tetradecanoylphorbol-13-acetate (TPA) known to differentiate SH-SY5Y cells into a neuronal phenotype and to increase NPY expression through activation of protein kinase C (PKC) was applied as a positive control (16. nM). Cell viability after drug treatment was tested with a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. NPY expression was measured using immunofluorescence and quantitative RT-PCR (qRT-PCR). Results from immunocytochemistry have shown NPY levels to be significantly increased following a 72. h but not 24. h VPA treatment. A further increase in expression was observed with simultaneous VPA and TPA treatment, suggesting that the two agents may increase NPY expression through different mechanisms. The increase in NPY mRNA by VPA and TPA was confirmed with qRT-PCR after 72. h. In contrast, AMI had no effect on NPY expression in SH-SY5Y cells.Together, the data point to an elevation of human NPY mRNA and peptide levels by therapeutic concentrations of VPA following chronic treatment. Thus, upregulation of NPY may have an impact in anti-cancer treatment of neuroblastomas with VPA, and antagonizing hypothalamic NPY effects may help to ameliorate VPA-induced weight gain and obesity without interfering with the desired central effects of VPA.",
author = "Farrelly, {Lorna A.} and Savage, {Niall T P} and Cristina O'Callaghan and Andr{\'e} Toulouse and Yilmazer-Hanke, {Deniz M.}",
year = "2013",
doi = "10.1016/j.regpep.2013.08.005",
language = "English",
volume = "186",
pages = "123--130",
journal = "Regulatory Peptides",
issn = "0167-0115",
publisher = "Elsevier",

}

TY - JOUR

T1 - Therapeutic concentrations of valproate but not amitriptyline increase neuropeptide Y (NPY) expression in the human SH-SY5Y neuroblastoma cell line

AU - Farrelly, Lorna A.

AU - Savage, Niall T P

AU - O'Callaghan, Cristina

AU - Toulouse, André

AU - Yilmazer-Hanke, Deniz M.

PY - 2013

Y1 - 2013

N2 - Neuropeptide Y (NPY) is a peptide found in the brain and autonomic nervous system, which is associated with anxiety, depression, epilepsy, learning and memory, sleep, obesity and circadian rhythms. NPY has recently gained much attention as an endogenous antiepileptic and antidepressant agent, as drugs with antiepileptic and/or mood-stabilizing properties may exert their action by increasing NPY concentrations, which in turn can reduce anxiety and depression levels, dampen seizures or increase seizure threshold.We have used human neuroblastoma SH-SY5Y cells to investigate the effect of valproate (VPA) and amitriptyline (AMI) on NPY expression at therapeutic plasma concentrations of 0.6. mM and 630. nM, respectively. In addition, 12-O-tetradecanoylphorbol-13-acetate (TPA) known to differentiate SH-SY5Y cells into a neuronal phenotype and to increase NPY expression through activation of protein kinase C (PKC) was applied as a positive control (16. nM). Cell viability after drug treatment was tested with a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. NPY expression was measured using immunofluorescence and quantitative RT-PCR (qRT-PCR). Results from immunocytochemistry have shown NPY levels to be significantly increased following a 72. h but not 24. h VPA treatment. A further increase in expression was observed with simultaneous VPA and TPA treatment, suggesting that the two agents may increase NPY expression through different mechanisms. The increase in NPY mRNA by VPA and TPA was confirmed with qRT-PCR after 72. h. In contrast, AMI had no effect on NPY expression in SH-SY5Y cells.Together, the data point to an elevation of human NPY mRNA and peptide levels by therapeutic concentrations of VPA following chronic treatment. Thus, upregulation of NPY may have an impact in anti-cancer treatment of neuroblastomas with VPA, and antagonizing hypothalamic NPY effects may help to ameliorate VPA-induced weight gain and obesity without interfering with the desired central effects of VPA.

AB - Neuropeptide Y (NPY) is a peptide found in the brain and autonomic nervous system, which is associated with anxiety, depression, epilepsy, learning and memory, sleep, obesity and circadian rhythms. NPY has recently gained much attention as an endogenous antiepileptic and antidepressant agent, as drugs with antiepileptic and/or mood-stabilizing properties may exert their action by increasing NPY concentrations, which in turn can reduce anxiety and depression levels, dampen seizures or increase seizure threshold.We have used human neuroblastoma SH-SY5Y cells to investigate the effect of valproate (VPA) and amitriptyline (AMI) on NPY expression at therapeutic plasma concentrations of 0.6. mM and 630. nM, respectively. In addition, 12-O-tetradecanoylphorbol-13-acetate (TPA) known to differentiate SH-SY5Y cells into a neuronal phenotype and to increase NPY expression through activation of protein kinase C (PKC) was applied as a positive control (16. nM). Cell viability after drug treatment was tested with a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. NPY expression was measured using immunofluorescence and quantitative RT-PCR (qRT-PCR). Results from immunocytochemistry have shown NPY levels to be significantly increased following a 72. h but not 24. h VPA treatment. A further increase in expression was observed with simultaneous VPA and TPA treatment, suggesting that the two agents may increase NPY expression through different mechanisms. The increase in NPY mRNA by VPA and TPA was confirmed with qRT-PCR after 72. h. In contrast, AMI had no effect on NPY expression in SH-SY5Y cells.Together, the data point to an elevation of human NPY mRNA and peptide levels by therapeutic concentrations of VPA following chronic treatment. Thus, upregulation of NPY may have an impact in anti-cancer treatment of neuroblastomas with VPA, and antagonizing hypothalamic NPY effects may help to ameliorate VPA-induced weight gain and obesity without interfering with the desired central effects of VPA.

UR - http://www.scopus.com/inward/record.url?scp=84884178223&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884178223&partnerID=8YFLogxK

U2 - 10.1016/j.regpep.2013.08.005

DO - 10.1016/j.regpep.2013.08.005

M3 - Article

VL - 186

SP - 123

EP - 130

JO - Regulatory Peptides

JF - Regulatory Peptides

SN - 0167-0115

ER -