Cholecystokinin levels in prohormone convertase 2 knock-out mouse brain regions reveal a complex phenotype of region-specific alterations.
Prohormone convertase 2 is widely co-localized with cholecystokinin in rodent brain. To examine its role in cholecystokinin processing, cholecystokinin levels were measured in dissected brain regions from prohormone convertase 2 knock-out mice. Cholecystokinin levels were lower in hippocampus, septum, thalamus, mesencephalon, and pons in knock-out mice than wild-type mice. In cerebral cortex, cortex-related structures and olfactory bulb, cholecystokinin levels were higher than wild type. Female mice were more affected by the loss of prohormone convertase 2 than male mice. The decrease in cholecystokinin levels in these brain regions shows that prohormone convertase 2 is important for cholecystokinin processing. Quantitative polymerase chain reaction measurements were performed to examine the relationship between peptide levels and cholecystokinin and enzyme expression. They revealed that cholecystokinin and prohormone convertase 1 mRNA levels in cerebral cortex and olfactory bulb were actually lower in knock-out than wild type, whereas their expression in other brain regions of knock-out mouse brain was the same as wild type. Female mice frequently had higher expression of cholecystokinin and prohormone convertase 1, 2, and 5 mRNA than male mice. The loss of prohormone convertase 2 alters CCK processing in specific brain regions. This loss also appears to trigger compensatory mechanisms in cerebral cortex and olfactory bulb that produce elevated levels of cholecystokinin but do not involve increased expression of cholecystokinin, prohormone convertase 1 or 5 mRNA.
Beinfeld
Margery C
MC
Departments of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts 02111, USA. Margery.beinfeld@tufts.edu
Blum
Alissa
A
Vishnuvardhan
Daesety
D
Fanous
Sanya
S
Marchand
James E
JE
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002268:Carboxypeptidases / Q000737:chemistry; D002540:Cerebral Cortex / Q000378:metabolism; D002766:Cholecystokinin / Q000096:biosynthesis* / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005838:Genotype; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009830:Olfactory Bulb / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D045664:Proprotein Convertase 1 / Q000378:metabolism; D045706:Proprotein Convertase 2 / Q000235:genetics* / Q000502:physiology*; D045702:Proprotein Convertase 5 / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D014018:Tissue Distribution; D014357:Trypsin / Q000737:chemistry
D012333:RNA, Messenger; D012313:RNA; D002766:Cholecystokinin; D002268:Carboxypeptidases; D045702:Proprotein Convertase 5; C473805:propeptide convertase 5, mouse; D014357:Trypsin; D045664:Proprotein Convertase 1; D045706:Proprotein Convertase 2