PMID- 23702255 OWN - NLM STAT- MEDLINE DCOM- 20140207 LR - 20160415 IS - 1532-2785 (Electronic) IS - 0143-4179 (Linking) VI - 47 IP - 4 DP - 2013 Aug TI - Cholecystokinin-8 induces brain-derived neurotrophic factor expression in noradrenergic neuronal cells. PG - 245-50 LID - S0143-4179(13)00025-5 [pii] LID - 10.1016/j.npep.2013.04.002 [doi] 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 (10 nM) elevates BDNF levels time-dependently and by 1.82-fold after 4h of incubation. In addition, pretreatment with CCK-8S reversed H(2)O(2) (100 muM)-mediated down-regulation of BDNF expression, and effectively suppressed H(2)O(2)-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-1alpha (PGC-1alpha). 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. CI - Copyright (c) 2013 Elsevier Ltd. All rights reserved. FAU - Hwang, Cheol Kyu AU - Hwang CK AD - Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. FAU - Kim, Do Kyung AU - Kim DK FAU - Chun, Hong Sung AU - Chun HS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130520 PL - Netherlands TA - Neuropeptides JT - Neuropeptides JID - 8103156 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Peptide Fragments) RN - 0 (cholecystokinin 8) RN - 9011-97-6 (Cholecystokinin) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Adrenergic Neurons/*drug effects/metabolism MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Caspase 3/metabolism MH - Cell Line MH - Cholecystokinin/*pharmacology MH - Down-Regulation/drug effects MH - Hydrogen Peroxide/pharmacology MH - Membrane Potentials/drug effects MH - Mice MH - Peptide Fragments/*pharmacology MH - Signal Transduction/drug effects EDAT- 2013/05/25 06:00 MHDA- 2014/02/08 06:00 CRDT- 2013/05/25 06:00 PHST- 2012/12/13 00:00 [received] PHST- 2013/04/05 00:00 [revised] PHST- 2013/04/18 00:00 [accepted] PHST- 2013/05/25 06:00 [entrez] PHST- 2013/05/25 06:00 [pubmed] PHST- 2014/02/08 06:00 [medline] AID - S0143-4179(13)00025-5 [pii] AID - 10.1016/j.npep.2013.04.002 [doi] PST - ppublish SO - Neuropeptides. 2013 Aug;47(4):245-50. doi: 10.1016/j.npep.2013.04.002. Epub 2013 May 20.