Disease relevance of PGC

• Infection from Helicobacter pylori significantly influences pepsinogen A (PGA) and C (PGC) levels in serum [1].
• A significant association was found between cagA and raised serum PGC levels in patients with antral gastritis but not in patients with peptic ulcer [1].
• AIM: To identify a molecular marker for gastric cancer, and to investigate the relationship between the polymorphism of pepsinogen C (PGC) gene and the genetic predisposition to gastric cancer [2].
• Precursors of the gastric proteases pepsinogen A (pepsinogen I) and pepsinogen C (pepsinogen II) and slow-moving protease were demonstrated in biopsy specimens from Barrett's epithelium in 21 of 22 patients with Barrett's esophagus; in 14 of them, in variable combinations at different sites [3].
• On the basis of these results, we suggest that pepsinogen C expression by human mammary epithelium may be involved in the development of breast diseases, being also of potential interest as a biochemical marker of the hormonal imbalance underlying these pathologies [4].

Psychiatry related information on PGC

• As expected, men who reported overall change in frequency of social interaction scored substantially lower on the PGC Morale Scale than those who perceived no change [5].
• Data on 150 people, between the ages of 50 and 82, yielded high correlations between three measures of well-being (the MUNSH, the LSI-Z, and the PGC) and the Edwards Social Desirability Scale, but only moderate ones between well-being scales and the Marlowe-Crowne Social Desirability Scale [6].

High impact information on PGC

• The maintenance of germline-like methylation with a switch in PGC fate is somewhat analogous to the situation in lag mutants from Volvox, which retain large gonidial-sized cells that can nevertheless initiate somatic differentiation [7].
• Basal serum gastrin, serum pepsinogen A, and serum pepsinogen C concentrations were monitored at regular intervals [8].
• Human gastric mucosa contains three immunochemically distinguishable aspartic proteinases, pepsinogen I (pepsinogen A), pepsinogen II (pepsinogen C, progastricsin), and a nonpepsinogen proteinase also termed slow moving proteinase (SMP) [9].
• Based on their origin and demonstrated properties, these human PGC-derived cultures meet the criteria for pluripotent stem cells and most closely resemble EG cells [10].
• PURPOSE: Here we evaluate in breast cancer patients the prognostic value of pepsinogen C, a proteolytic enzyme involved in the digestion of proteins in the stomach that is also synthesized by a significant percentage of breast carcinomas [11].

Chemical compound and disease context of PGC

• Studies using nifedipine with both the unilaterally nephrectomized DOCA salt rat model and the 1 5/6 nephrectomy model demonstrated reduced proteinuria and glomerulosclerosis that was independent of reduced PGC [12].
• Patients cured of H. pylori infection showed a significant decrease in the histological activity of both antral and body gastritis (P< 0.0001), a significant drop in immunoglobulin (Ig) G anti-H. pylori antibodies (P< 0.0001) and pepsinogen (PG) C (P<0.0001) and an increase in the PGA/PGC ratio (P<0.0001) [13].
• CONCLUSIONS: The 7 day, lansoprazole-based triple therapy was well tolerated and highly effective in the cure of H. pylori infection, the reduction of symptoms, chronic gastritis activity and serum levels of IgG anti-H. pylori antibodies and PGC [13].
• Hormonal regulation of the human pepsinogen C gene in breast cancer cells. Identification of a cis-acting element mediating its induction by androgens, glucocorticoids, and progesterone [14].
• Reverse transcription-polymerase chain reaction analysis in a series of breast cancer cell lines confirmed the amplification of pepsinogen C mRNA after induction with dihydrotestosterone, in those cells expressing the androgen receptor mRNA [14].

Biological context of PGC

• In order to explain the low fractional clearance of PGC compared with that of PGA and the less marked effect of arginine or lysine infusion on the fractional clearance of PGC, an additional PGC-specific binding site has to be postulated [15].
• The PGC gene was localized to human chromosome 6 by analysis of a panel of human x mouse somatic cell hybrids [16].
• The 10.7-kb PGC gene includes nine exons and exhibits a high degree of sequence identity (60%) with the functionally related pepsinogen A genes [17].
• The aim of our study was to assess the influence of cagA genotype on circulating levels of PGA and PGC [1].
• The polymorphism of PGC gene was detected by polymerase chain reaction (PCR) and the relation between the genetic polymorphism of PGC and gastric cancer was examined [2].

Anatomical context of PGC

• Northern analysis of gastric mucosa poly(A+) RNA with a PGC cDNA probe revealed an mRNA 1.5-kilobase species that was indistinguishable from that detected with a human pepsinogen A (PGA) cDNA probe [16].
• We used this assay to measure pepsinogen C in seminal plasma, breast cyst fluid, amniotic fluid, male and female serum, serum from patients with prostate cancer, urine, breast tumor cytosolic extracts, breast milk, and cerebrospinal fluid [18].
• Highest pepsinogen C concentrations were in seminal plasma, followed by breast cyst fluid and amniotic fluid [18].
• In normal human tissues, pepsinogen A mRNA was expressed only in the fundic mucosa of the stomach, whereas pepsinogen C mRNA was expressed in all regions of the stomach mucosa and also in the proximal duodenal mucosa [19].
• OBJECTIVE: To compare prognostic results in patients with gastric stump cancer (GSC) versus those with primary gastric cancer (PGC) [20].

Associations of PGC with chemical compounds

• Urea-containing polyacrylamide gel electrophoresis of the eluted material consistently revealed two main signals of 35S radioactivity (one with an M(r) between 600,000 and 750,000 [PGA] and the other with an M(r) between 120,000 and 180,000 [PGC]) [21].
• Several different collection strategies were tested, using a selection of liquids (methanol, toluene, methyl tert-butyl ether, acetonitrile), inert and solid-phase extraction materials (Nexus, Oasis, LiChrolut), and 1-cm liquid chromatography precolumns (porous graphitic carbon, PGC) [22].
• 3. In contrast, PRA was lower in the PGC diabetic patients (1.3 +/- 0.3 pmol of angiotensin 1 h-1 ml-1) compared with the other groups (2.5 +/- 0.5 and 2.1 +/- 0.2 pmol of angiotensin I h-1 ml-1, P less than 0.05) [23].
• The most striking result was a significantly higher promoter methylation frequency of O6-methylguanine methyl transferase (MGMT) in BC compared with JC and PGC (0.7 vs. 0.08 vs. 0.29, respectively; p = 0.011; methylation exclusively in tumors), confirmed immunohistochemically by a significant loss of MGMT protein in BC (p = 0.006) [24].
• Eight serum and urine samples were obtained after raising the serum PGA and PGC levels by oral administration of omeprazole [25].

Regulatory relationships of PGC

• The proteolytic activity of PA-PGC was used for digesting the blocking reagent around the target antigen (in situ digestion method) or casein-clotting in the agarose plate containing skimmed milk (caseogram print method) [26].

Other interactions of PGC

• The concentrations of PGA, PGC, and gastrin were measured by radioimmunoassays [27].
• The human digestive enzyme gastricsin (pepsin C) is an aspartic proteinase that is synthesized as the inactive precursor (zymogen) progastricsin (pepsinogen C or hPGC) [28].
• Following resolution by PGC chromatography, MALDI-MS in conjunction with alkaline phosphatase treatment identified Ser(555), Ser(556), Ser(724), and Ser(727) as sites of phosphorylation on MLK3 [29].
• The well-orchestrated expression of the multitude of proteins involved in these adaptations is mediated by the rapid activation of PPAR gamma co-activator (PGC) 1, a protein that binds to various transcription factors to maximize transcriptional activity [30].
• Frequencies of p16INK4a promoter methylation were 0.5 (BC), 0.42 (JC) and 0.29 (PGC; n.s.), but methylation was almost absent in NT controls [24].

Analytical, diagnostic and therapeutic context of PGC

• Immunofluorometric assay of pepsinogen C and preliminary clinical applications [18].
• The Abs were used to construct a two-site sandwich-type assay for pepsinogen C with time-resolved fluorometry as a detection technique [18].
• PURPOSE: we investigated by immunohistochemistry the pepsinogen C (pepC) expression in uveal melanomas and analyzed the possible relationship to clinicopathological parameters and prognostic significance [31].
• The relation between serum levels of pepsinogen A (PGA) and pepsinogen C (PGC) and endoscopic findings in association with short-term NSAID use was investigated in two double-blind, crossover studies in healthy volunteers [32].
• CONCLUSION: The prognosis after resection and adequate lymphadenectomy does not differ between patients with GSC and PGC [20].

References