Disease relevance of PRSS3

• As epigenetic alteration is common in non-small cell lung cancer (NSCLC), we sought to determine if promoter hypermethylation of PRSS3 occurred in this disease, and if it was associated with clinical features of NSCLC or tobacco-related exposures in these patients [1].
• The serine protease family member PRSS3 (trypsinogen-IV) has been implicated as a putative tumor suppressor gene due to its loss of expression, which is correlated with promoter hypermethylation, in esophageal squamous cell carcinoma and gastric adenocarcinoma [1].
• Furthermore, the findings raise the possibility that inappropriate activation of mesotrypsinogen in the pancreas might lower protective SPINK1 levels and contribute to the development of human pancreatitis [2].
• CONCLUSION: The results classify E32del mesotrypsinogen as a frequent polymorphic variant, which is not associated with chronic alcoholic pancreatitis [3].
• METHODS: We screened 97 German patients with chronic pancreatitis of alcoholic etiology and 109 healthy controls for the presence of the E32del variant and characterized the biochemical properties of E32del mesotrypsinogen [3].
• Trypsin IV and p23 caused thermal hyperalgesia and mechanical allodynia and hyperalgesia in mice, and these effects were absent in PAR (-/-)(2) mice but maintained in PAR (-/-)(1) mice [4].

Psychiatry related information on PRSS3

• Clot initiation (R, reaction time), propagation (MTG, maximum thrombus generation), and strength (MG, maximum elastic modulus) were determined [5].

High impact information on PRSS3

• Its electrophoretic mobility and isoelectric pH lie between those of the cationic and anionic trypsinogen variants, and we propose the name "mesotrypsinogen" for the new enzyme precursor [6].
• In the right temporal lobe, the activation was located in the MTG/STS (lower bank) [7].
• Exposure of cell lines expressing PAR(2) and PAR(4) to trypsin IV increased [Ca(2+)](i) and strongly desensitized cells to PAR agonists, whereas there were no responses in cells lacking these receptors [8].
• In this regard, it is noteworthy that the well known pathological trypsinogen activator cathepsin B exhibited a preference for the activation of mesotrypsinogen of all three human trypsinogen isoforms, suggesting a biochemical mechanism for mesotrypsinogen activation in pancreatic acinar cells [2].
• Here, we report a variation of the theme of new gene creation by duplication: the PRSS3 gene was formed by segmental duplications originating from chromosomes 7q35 and 11q24 [9].

Chemical compound and disease context of PRSS3

• Background:The [(13)C]mixed triacylglycerol (MTG) breath test is a non-invasive measure of fat digestion and can be used to assess the need for enzyme replacement therapy in children with cystic fibrosis (CF) [10].
• Activating transcription factor 3, heat shock protein 70, heat shock protein 27, and mesotrypsinogen were increased, whereas pancreatitis associate protein, folate carrier, and metallothionein were decreased [11].

Biological context of PRSS3

• On the other hand, the high prevalence of this alteration makes PRSS3 methylation an attractive biomarker for use in diagnostic or screening applications in NSCLC [1].
• Epigenetic silencing of the PRSS3 putative tumor suppressor gene in non-small cell lung cancer [1].
• Arsenic exposure, measured as toenail arsenic, was associated with RASSF1A (P < 0.02) and PRSS3 (P < 0.1) but not p16(INK4A) or SFRP promotor methylation, in models adjusted for stage and other risk factors [12].
• Histology also showed that MTG implanted cells grew as vascularized solid tumors compared to GM tumors which formed cysts [13].

Anatomical context of PRSS3

• Mesotrypsin (trypsin IV), in contrast to cationic and anionic trypsin, cannot activate or disable PARs in human epithelial cells, demonstrating that the receptors are no substrates for this isoenzyme [14].
• Age-associated minicolumn thinning was found in temporal lobe association cortex (Tpt and MTG) but not primary auditory cortex (HG) [15].
• Tumor cells injected subcutaneously in the flank using either Matrigel (MTG, an extract of basement membrane proteins) or growth medium (GM) as a vehicle were compared [13].
• When NR-stained lipid droplets were specifically bleached, a significant increase in the MTG signal in stained mitochondria was observed (FRET efficiency, E=22.2 +/- 3.18%) [16].
• Immature and in vitro-matured porcine oocytes were stained with Mitotracker Green (MTG; mitochondria) and Nile Red (NR; lipid droplets) [16].

Associations of PRSS3 with chemical compounds

• Here we report the X-ray structure of human trypsin IV in complex with the inhibitor benzamidine at 1.7 A resolution [17].
• The (13)C-mixed triacylglcerol (MTG, 1,3-distearyl, 2-[1-(13)C]octanoyl glycerol) breath test is a non-invasive measure of intraluminal fat digestion [18].
• We measured the minicolumn spacing and organization of cells in Heschl's gyrus (primary auditory cortex, A1), the Planum Temporale (Tpt, BA22), and middle temporal gyrus (MTG, BA21) of 17 normally aged human adults [15].
• Glucose uptake (M) value negatively correlated with the MTG level (R2 = -.56, P < .0001), which was increased in obese patients (11.6 +/- 2.2 v 6.2 +/- 1.4 micromol/g wet weight muscle tissue, P < .0001) [19].
• In general, the DTIs tested prolonged R in a concentration-dependent fashion but did not diminish MTG or MG nearly as well as heparin [5].

Other interactions of PRSS3

• Epigenetic silencing of RASSF1A and PRSS3 and any of the SFRP genes were each significantly associated with advanced tumor stage (P < 0.001, P < 0.04, and P < 0.005, respectively) [12].
• Trypsin-I, trypsin-IIA and trypsin-III showed preference for Arg over Lys, but responded differently to proteinaceous or synthetic inhibitors [20].

Analytical, diagnostic and therapeutic context of PRSS3

• Using methylation-specific PCR, we determined the promoter hypermethylation status of PRSS3 in a case series study of primary NSCLC, and found methylation of this gene to be common, occurring in 53% (86 of 166) of tumors examined [1].
• Specific peptidyl linkers that result in the heterodimerization of functional proteins, which is catalyzed by microbial transglutaminase from Streptomyces mobaraensis (MTG), were generated based on a ribonuclease S-peptide using site-directed mutagenesis [21].
• With supernatants from high-speed centrifugation of HBT biopsies or the human breast cancer cell line MCF-7, reducing agents increased the apparent E2R binding in the order: DTT greater than G-SH greater than MTG [22].

References