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 (10 nM) elevates BDNF levels time-dependently and by 1.82-fold after 4h of incubation. In addition, pretreatment with CCK-8S reversed H₂O₂ (100 μM)-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.
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
authors.forename: Cheol Kyu
authors.initials: CK
authors.lastname: Hwang
authors.forename: Do Kyung
authors.initials: DK
authors.lastname: Kim
authors.forename: Hong Sung
authors.initials: HS
authors.lastname: Chun
mesh_terms: D059331:Adrenergic Neurons / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002766:Cholecystokinin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D010446:Peptide Fragments; C410885:cholecystokinin 8; D002766:Cholecystokinin; D006861:Hydrogen Peroxide; D053148:Caspase 3