Altered processing of procholecystokinin in carboxypeptidase E‐deficient fat mice: differential synthesis in neurons and endocrine cells

FEBS Letters

Lacourse, Karen A¹  Friis-Hansen, Lennart¹  Rehfeld, Jens F²  Samuelson, Linda C¹ 

[1] Department of Physiology, University of Michigan, Ann Arbor, MI 48109-0622, USA;Department of Clinical Biochemistry, Rigshospitalet, DK-2100 Copenhagen, Denmark

关键词: Cholecystokinin;    Prohormone processing;    Carboxypeptidase E;    Obesity;    fat mouse;    CCK;    cholecystokinin;    CPE;    carboxypeptidase E;    RIA;    radioimmunoassay;   

DOI  :  10.1016/S0014-5793(98)01099-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The fat mouse strain exhibits a late-onset obesity syndrome associated with a mutation in the gene encoding carboxypeptidase E (CPE). CPE plays a central role in the biosynthesis of many regulatory peptides. Therefore, we examined the processing of procholecystokinin (proCCK) in the brain (neurons) and small intestine (endocrine cells) of fat/fat mice. In the brain, bioactive CCK was markedly reduced (7.9±1.0 pmol/g in fat/fat mice vs. 82.5±11.2 pmol/g in controls), but the concentration of the CPE substrate, glycyl-arginine-extended CCK, was elevated 105-fold. In contrast, the concentration of bioactive CCK in intestinal endocrine cells was unaffected. Endocrine cell processing was, nevertheless, altered with a 33-fold increase in glycyl-arginine-extended CCK. Interestingly, although total proCCK products were normal in the brain they were elevated 3-fold in the intestine, indicating that biosynthesis is upregulated in endocrine cells but not neurons to compensate for the processing defect. These results demonstrate that the CPE mutation differentially affects CCK processing in these two cell types. Intestinal CCK synthesis more closely resembles progastrin processing, suggesting the presence of an endocrine-specific biosynthetic regulatory mechanism not present in neurons.

【 授权许可】

Unknown