Expression of PCSK1 (PC1/3), PCSK2 (PC2) and PCSK3 (furin) in mouse small intestine

Gagnon, Jeffrey; Mayne, Janice; Mbikay, Majambu; Woulfe, John; Chrétien, Michel

doi:10.1016/j.regpep.2008.07.006

Cited by 34 publications

(28 citation statements)

References 30 publications

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“…As expected from reports in other species (i.e. Gagnon et al, 2009) and according to the fundamental function of PCSK1 in processing key-gut/intestine prohormones (Zhu et al, 2006), gastric oxyntic mucosa showed a qualitatively higher level of PCSK1gene expression compared with the other tissues ( Figure S1). Therefore, qPCR was used to precisely evaluate the level of expression of this gene in weaning pigs and to evaluate its association with PCSK1 SNPs (see below).…”

Section: Gene Expression Analysessupporting

confidence: 86%

Polymorphisms in an obesity-related gene (PCSK1) are associated with fat deposition and production traits in Italian heavy pigs

Bertolini

Scotti

Trevisi

et al. 2012

Animal

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The proprotein convertase subtilisin/kexin type 1 (PCSK1) gene encodes the prohormone convertase 1/3 enzyme that processes prohormones into functional hormones that, in turn, regulate central and peripheral energy metabolism. Mutations in the human PCSK1 gene cause severe monogenic obesity or confer risk of obesity. We herein investigated the porcine PCSK1 gene with the aim of identifying polymorphisms associated with fat deposition and production traits in Italian heavy pigs. By re-sequencing about 5.1 kb of this gene in 21 pigs of different breeds, we discovered 14 polymorphisms that were organized in nine haplotypes, clearly distributed in two clades of putative European and Asian origin. Then we re-mapped this gene on porcine chromosome 2 and analysed its expression in several tissues including gastric oxyntic mucosa of weanling pigs in which PCSK1 processes the pre-pro-ghrelin into ghrelin, which in turn is involved in the control of feed intake and energy metabolism. Association analyses between PCSK1 single-nucleotide polymorphisms (SNPs) and production, carcass and several other traits were conducted on five groups of pigs from three different experimental designs, for a total of 1221 animals. Results indicated that the analysed SNPs were associated (P , 0.01 or P , 0.05) with several traits including backfat thickness and visible intermuscular fat in Italian Duroc (ID) and growth performances in Italian Large White (ILW) and in ILW 3 Italian Landrace pigs. However, the effects estimated in the ILW were opposite to the effects reported in the ID pigs. Suggestive association (P , 0.10) was observed with muscle cathepsin B activity, opening, if confirmed, potential applications to reduce the excessive softness defect of the green hams that is of particular concern for the processing industry. The results obtained supported the need to further investigate the PCSK1 gene to fully exploit the value of its variability and apply this information in pig breeding programmes.

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Section: Gene Expression Analysessupporting

confidence: 86%

Polymorphisms in an obesity-related gene (PCSK1) are associated with fat deposition and production traits in Italian heavy pigs

Bertolini

Scotti

Trevisi

et al. 2012

Animal

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“…Differential posttranslational processing resulting in multiple products has been described for other peptides such as somatostatin, gastrin, and cholecystokinin (CCK) (4,23). In addition, the uneven distribution of varying forms of gastrin and CCK throughout the small intestine supports the notion of a nonuniform expression of posttranslational processing enzymes in the gut (11,23). Our findings of increased expression of the COOH-terminal truncated form of GIP in the distal gut relative to proximal regions also suggests a nonuniform expression of the enzymes involved in pro-GIP processing.…”

Section: Discussionmentioning

confidence: 96%

“…In previous studies Gagnon et al (11) reported that the majority of K cells express furin, leading them to conclude that furin might be involved in pro-GIP processing. In contrast, Ugleholdt et al (39) reported that PC1/3 is essential and sufficient for processing pro-GIP to GIP and also that pro-GIP processing is impaired in PC1/3-null mice.…”

Section: Discussionmentioning

confidence: 99%

“…Furin is a member of the proprotein convertase subtilisin/kexin (PCSK) family that is reportedly present in the majority of GIP-positive cells in wild-type mouse intestine (11). To further explore whether furin is potentially involved in pro-GIP processing, we examined the colocalization of furin with GIP in wild-type mouse intestine using three different anti-furin antibodies.…”

Section: Furin Is Likely Not Involved In Pro-gip Processingmentioning

confidence: 99%

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Differential processing of pro-glucose-dependent insulinotropic polypeptide in gut

Fujita

Asadi

Yang

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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Glucose-dependent insulinotropic polypeptide (GIP) is a hormone released from enteroendocrine K cells in response to meals. Posttranslational processing of the precursor protein pro-GIP at residue 65 by proprotein convertase subtilisin/kexin type 1 (PC1/3) in gut K cells gives rise to the established 42-amino-acid form of GIP (GIP1–42). However, the pro-GIP peptide sequence contains a consensus cleavage site for PC2 at residues 52–55 and we identified PC2 immunoreactivity in a subset of K cells, suggesting the potential existence of a COOH-terminal truncated GIP isoform, GIP1–30. Indeed a subset of mouse and human K cells display GIP immunoreactivity with GIP antibodies directed to the mid portion of the peptide, but not with a COOH-terminal-directed GIP antibody, indicative of the presence of a truncated form of GIP. This population of cells represents ∼5–15% of the total GIP-immunoreactive cells in mice, depending on the region of intestine, and is virtually absent in mice lacking PC2. Amidated GIP1–30 and GIP1–42 have comparable potency at stimulating somatostatin release in the perfused mouse stomach. Therefore, GIP1–30 represents a naturally occurring, biologically active form of GIP.

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“…23,24 It is also found in peripheral endocrine tissues, most particularly in the pancreas 25,26 and the intestine. 27 In these organs, it mediates the production of a wide variety of appetite-controlling peptides. Comparative proteomics of the pituitary and hypothalamic extracts from WT and PCSK2-deficient mice have shown that several precursors to these peptides are either unprocessed or aberrantly processed.…”

Section: Discussionmentioning

confidence: 99%

Genetic deficiency for proprotein convertase subtilisin/kexin type 2 in mice is associated with decreased adiposity and protection from dietary fat-induced body weight gain

et al. 2010

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Background: Proprotein convertase subtilisin/xexin type 2 (PCSK2) is an endoproteinase responsible for proteolytic activation of a number of precursors to active neuropeptides and peptide hormones, known to influence glucose homeostasis, food intake and ultimately body mass. In this study, we examined the consequences of PCSK2 deficiency on these phenotypic traits. Study Design: Weight gain with age under diets of different fat contents was monitored. White adipose tissue (WAT) and muscle masses were evaluated. Plasma levels of triglycerides, leptin, ghrelin, insulin and proglucagon-derived peptides were measured as well as leptin and acetyl coenzyme-a carboxylase (ACCa) mRNA levels in adipose tissue. Results: Compared with their Pcsk2þ / þ littermates, Pcsk2 À/À mice weighed significantly less as weanlings and as adults. As adults, they carried noticeably less fat mass, with similar lean muscle mass: their plasma leptin level and adipose tissue leptin mRNA level were accordingly lower. PCSK2 deficiency did not affect food intake or the level of the orexigenic hormone ghrelin. However, PCSK2 deficiency resulted in decreased plasma triglycerides and reduced ACCa mRNA levels in WAT. Interestingly, unlike their Pcsk2 þ / þ littermates, Pcsk2 À/À were resistant to enhanced body weight gain when fed a high-fat diet. Consistent with a role of PCSK2 in body mass gain, diet-induced or genetically obese mice were found to contain significantly higher levels of PCSK2 mRNA in their brain and stomach than their lean counterparts. Conclusion: Collectively, these results suggest that PCSK2 contributes to increase in body mass through the various regulatory peptides generated through its action. It represents a potential target in the prevention and treatment of obesity.

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Expression of PCSK1 (PC1/3), PCSK2 (PC2) and PCSK3 (furin) in mouse small intestine

Cited by 34 publications

References 30 publications

Polymorphisms in an obesity-related gene (PCSK1) are associated with fat deposition and production traits in Italian heavy pigs

Polymorphisms in an obesity-related gene (PCSK1) are associated with fat deposition and production traits in Italian heavy pigs

Differential processing of pro-glucose-dependent insulinotropic polypeptide in gut

Genetic deficiency for proprotein convertase subtilisin/kexin type 2 in mice is associated with decreased adiposity and protection from dietary fat-induced body weight gain

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