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

Cheol Kyu Hwang, Do Kyung Kim, Hong Sung Chun

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11 Scopus citations


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 languageEnglish (US)
Pages (from-to)245-250
Number of pages6
Issue number4
StatePublished - Aug 2013

Bibliographical note

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


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


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