Cholecystokinin-8 induces brain-derived neurotrophic factor expression in noradrenergic neuronal cells

Cheol Kyu Hwang; Do Kyung Kim; Hong Sung Chun

doi:10.1016/j.npep.2013.04.002

Cholecystokinin-8 induces brain-derived neurotrophic factor expression in noradrenergic neuronal cells

Cheol Kyu Hwang, Do Kyung Kim, Hong Sung Chun

Pharmacology

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

The sulfated cholecystokinin octapeptide (CCK-8S) is one of the most abundant CCK fragment in the brain, but the effects of CCK-8S on locus coeruleus (LC) noradrenergic (NA) neuronal cells activity have not been studied. In this study, we investigated the effects of CCK-8S on the expression of brain-derived neurotrophic factor (BDNF) in LC NA neuronal cell line, LC3541. Results showed that CCK-8S (10nM) elevates BDNF levels time-dependently and by 1.82-fold after 4h of incubation. In addition, pretreatment with CCK-8S reversed H₂O₂ (100μM)-mediated down-regulation of BDNF expression, and effectively suppressed H₂O₂-induced caspase-3 activation. Furthermore, CCK-8S markedly induced expression of neuronal survival markers, such as extracellular signal-regulated kinase 1/2 (ERK 1/2), Akt/protein kinase B (PKB), Bcl-2, and peroxisome proliferators-activated receptor gamma coactivator-1α (PGC-1α). Pharmacological inhibitors of ERK 1/2, Akt/PKB, and protein kinase A (PKA) reversed CCK-8S-mediated BDNF induction in LC3541 cells. These results suggest the first evidence that CCK-8S can protect noradrenergic neurons and enhance the expression of BDNF via ERK 1/2-Akt/PKB-PKA-dependent pathways.

Original language	English (US)
Pages (from-to)	245-250
Number of pages	6
Journal	Neuropeptides
Volume	47
Issue number	4
DOIs	https://doi.org/10.1016/j.npep.2013.04.002
State	Published - Aug 2013

Bibliographical note

Funding Information:
This study was supported by research fund from Chosun University, 2013.

Keywords

Brain-derived neurotrophic factor
Cholecystokinin-8
Locus coeruleus
Noradrenergic neuron

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@article{dacefaa799ba45c1914a90be5ec3a984,

title = "Cholecystokinin-8 induces brain-derived neurotrophic factor expression in noradrenergic neuronal cells",

abstract = "The sulfated cholecystokinin octapeptide (CCK-8S) is one of the most abundant CCK fragment in the brain, but the effects of CCK-8S on locus coeruleus (LC) noradrenergic (NA) neuronal cells activity have not been studied. In this study, we investigated the effects of CCK-8S on the expression of brain-derived neurotrophic factor (BDNF) in LC NA neuronal cell line, LC3541. Results showed that CCK-8S (10nM) elevates BDNF levels time-dependently and by 1.82-fold after 4h of incubation. In addition, pretreatment with CCK-8S reversed H2O2 (100μM)-mediated down-regulation of BDNF expression, and effectively suppressed H2O2-induced caspase-3 activation. Furthermore, CCK-8S markedly induced expression of neuronal survival markers, such as extracellular signal-regulated kinase 1/2 (ERK 1/2), Akt/protein kinase B (PKB), Bcl-2, and peroxisome proliferators-activated receptor gamma coactivator-1α (PGC-1α). Pharmacological inhibitors of ERK 1/2, Akt/PKB, and protein kinase A (PKA) reversed CCK-8S-mediated BDNF induction in LC3541 cells. These results suggest the first evidence that CCK-8S can protect noradrenergic neurons and enhance the expression of BDNF via ERK 1/2-Akt/PKB-PKA-dependent pathways.",

keywords = "Brain-derived neurotrophic factor, Cholecystokinin-8, Locus coeruleus, Noradrenergic neuron",

author = "Hwang, {Cheol Kyu} and Kim, {Do Kyung} and Chun, {Hong Sung}",

note = "Funding Information: This study was supported by research fund from Chosun University, 2013.",

year = "2013",

month = aug,

doi = "10.1016/j.npep.2013.04.002",

language = "English (US)",

volume = "47",

pages = "245--250",

journal = "Neuropeptides",

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TY - JOUR

T1 - Cholecystokinin-8 induces brain-derived neurotrophic factor expression in noradrenergic neuronal cells

AU - Hwang, Cheol Kyu

AU - Kim, Do Kyung

AU - Chun, Hong Sung

N1 - Funding Information: This study was supported by research fund from Chosun University, 2013.

PY - 2013/8

Y1 - 2013/8

N2 - The sulfated cholecystokinin octapeptide (CCK-8S) is one of the most abundant CCK fragment in the brain, but the effects of CCK-8S on locus coeruleus (LC) noradrenergic (NA) neuronal cells activity have not been studied. In this study, we investigated the effects of CCK-8S on the expression of brain-derived neurotrophic factor (BDNF) in LC NA neuronal cell line, LC3541. Results showed that CCK-8S (10nM) elevates BDNF levels time-dependently and by 1.82-fold after 4h of incubation. In addition, pretreatment with CCK-8S reversed H2O2 (100μM)-mediated down-regulation of BDNF expression, and effectively suppressed H2O2-induced caspase-3 activation. Furthermore, CCK-8S markedly induced expression of neuronal survival markers, such as extracellular signal-regulated kinase 1/2 (ERK 1/2), Akt/protein kinase B (PKB), Bcl-2, and peroxisome proliferators-activated receptor gamma coactivator-1α (PGC-1α). Pharmacological inhibitors of ERK 1/2, Akt/PKB, and protein kinase A (PKA) reversed CCK-8S-mediated BDNF induction in LC3541 cells. These results suggest the first evidence that CCK-8S can protect noradrenergic neurons and enhance the expression of BDNF via ERK 1/2-Akt/PKB-PKA-dependent pathways.

AB - The sulfated cholecystokinin octapeptide (CCK-8S) is one of the most abundant CCK fragment in the brain, but the effects of CCK-8S on locus coeruleus (LC) noradrenergic (NA) neuronal cells activity have not been studied. In this study, we investigated the effects of CCK-8S on the expression of brain-derived neurotrophic factor (BDNF) in LC NA neuronal cell line, LC3541. Results showed that CCK-8S (10nM) elevates BDNF levels time-dependently and by 1.82-fold after 4h of incubation. In addition, pretreatment with CCK-8S reversed H2O2 (100μM)-mediated down-regulation of BDNF expression, and effectively suppressed H2O2-induced caspase-3 activation. Furthermore, CCK-8S markedly induced expression of neuronal survival markers, such as extracellular signal-regulated kinase 1/2 (ERK 1/2), Akt/protein kinase B (PKB), Bcl-2, and peroxisome proliferators-activated receptor gamma coactivator-1α (PGC-1α). Pharmacological inhibitors of ERK 1/2, Akt/PKB, and protein kinase A (PKA) reversed CCK-8S-mediated BDNF induction in LC3541 cells. These results suggest the first evidence that CCK-8S can protect noradrenergic neurons and enhance the expression of BDNF via ERK 1/2-Akt/PKB-PKA-dependent pathways.

KW - Brain-derived neurotrophic factor

KW - Cholecystokinin-8

KW - Locus coeruleus

KW - Noradrenergic neuron

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SN - 0143-4179

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JO - Neuropeptides

JF - Neuropeptides

IS - 4

ER -

Cholecystokinin-8 induces brain-derived neurotrophic factor expression in noradrenergic neuronal cells

Abstract

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