Pedtidomics of Cpefat/fat mouse hypothalamus -: Effect of food deprivation and exercise on peptide levels

被引:53
作者
Che, FY
Yuan, Q
Kalinina, E
Fricker, LD
机构
[1] Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA
[2] Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Prote, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China
关键词
D O I
10.1074/jbc.M411178200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Carboxypeptidase E is a major enzyme in the biosynthesis of numerous neuroendocrine peptides. Previously, we developed a technique for the isolation of neuropeptide-processing intermediates from mice that lack carboxypeptidase E activity Cpe(fat/fat) mice) due to a naturally occurring point mutation. In the present study, we used a differential labeling procedure with stable isotopic tags and mass spectrometry to quantitate the relative changes in a number of hypothalamic peptides in Cpe(fat/fat) mice in two different paradigms that each cause an similar to10% decrease in body mass. One paradigm involved a 2-day fast under normal sedentary conditions (i.e. standard mouse cages); the other involved giving mice access to an exercise wheel for 4 weeks with free access to food. Approximately 50 peptides were detected in both studies, and over 80 peptides were detected in at least one of the two studies. Twenty-eight peptides were increased >50% by food deprivation, and some of these were increased by 2- to 3-fold. In contrast, only three peptides were increased >50% in the group with exercise wheels, and many peptides showed a slight 15-30% decrease upon exercise. Approximately one-half of the peptides detected in both studies were identified by tandem mass spectrometry. Peptides found to be elevated by food deprivation but not exercise included a number of fragments of proenkephalin, prothyrotropin-releasing hormone, secretogranin II, chromogranin B, and pro-SAAS. Taken together, the differential regulation of these peptides in the two paradigms suggests that the regulation is not due to the lower body weight but to the manner in which the paradigms achieved this lower body weight.
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页码:4451 / 4461
页数:11
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