TY - JOUR
T1 - Cholecystokinin-2 receptor mediated gene expression in neuronal PC12 cells
AU - Hansen, Thomas v O
AU - Borup, Rehannah
AU - Marstrand, Troels
AU - Rehfeld, Jens F
AU - Nielsen, Finn C
N1 - Keywords: Animals; Cholesterol; Circadian Rhythm; Forskolin; Gene Expression Profiling; Gene Expression Regulation; Humans; Nerve Growth Factor; Neurons; Oligonucleotide Array Sequence Analysis; PC12 Cells; Plasminogen; Promoter Regions, Genetic; Rats; Receptor, Cholecystokinin B; Transfection
PY - 2007
Y1 - 2007
N2 - Cholecystokinin (CCK) is abundantly expressed in the CNS, in which it regulates feeding behavior and long-term memory. Moreover, CCK has been implicated in mental disorders, such as anxiety and schizophrenia. Despite its manifest physiological and pathophysiological role, the molecular targets of neuronal CCK are incompletely understood. To identify genes regulated by neuronal CCK, we generated neuronal PC12 cells stably expressing the CCK-2 receptor (CCK-2R) and treated the cells with sulphated CCK-8 for 2-16 h, before the global expression profile was examined. The changes in gene expression peaked after 2 h, with 67 differentially expressed transcripts identified. A pathway analysis indicated that CCK was implicated in the regulation of the circadian clock system, the plasminogen system and cholesterol metabolism. But transcripts encoding proteins involved in dopamine signaling, ornithine decarboxylase (ODC) regulation, memory and epidermal growth factor receptor (EGFR) signaling were also found. Several target genes contained cAMP response elements (CREs), serum response elements (SREs), activator protein 1 (AP1) elements and GC-rich regions, but otherwise no common regulatory promoter element could be identified. Comparison with forskolin- and nerve growth factor (NGF)-treated PC12 cells showed that CCK induced a separate set of target genes. Taken together, we propose that neuronal CCK may have a role in the regulation of the circadian rhythm, the metabolism of cerebral cholesterol and in the regulation of the plasminogen system.
AB - Cholecystokinin (CCK) is abundantly expressed in the CNS, in which it regulates feeding behavior and long-term memory. Moreover, CCK has been implicated in mental disorders, such as anxiety and schizophrenia. Despite its manifest physiological and pathophysiological role, the molecular targets of neuronal CCK are incompletely understood. To identify genes regulated by neuronal CCK, we generated neuronal PC12 cells stably expressing the CCK-2 receptor (CCK-2R) and treated the cells with sulphated CCK-8 for 2-16 h, before the global expression profile was examined. The changes in gene expression peaked after 2 h, with 67 differentially expressed transcripts identified. A pathway analysis indicated that CCK was implicated in the regulation of the circadian clock system, the plasminogen system and cholesterol metabolism. But transcripts encoding proteins involved in dopamine signaling, ornithine decarboxylase (ODC) regulation, memory and epidermal growth factor receptor (EGFR) signaling were also found. Several target genes contained cAMP response elements (CREs), serum response elements (SREs), activator protein 1 (AP1) elements and GC-rich regions, but otherwise no common regulatory promoter element could be identified. Comparison with forskolin- and nerve growth factor (NGF)-treated PC12 cells showed that CCK induced a separate set of target genes. Taken together, we propose that neuronal CCK may have a role in the regulation of the circadian rhythm, the metabolism of cerebral cholesterol and in the regulation of the plasminogen system.
U2 - 10.1111/j.1471-4159.2007.05076.x
DO - 10.1111/j.1471-4159.2007.05076.x
M3 - Journal article
C2 - 18028338
SN - 0022-3042
VL - 104
SP - 1450
EP - 1465
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 6
ER -