Disease relevance of Pdap1

• CONCLUSIONS: These observations show that the accumulated PAP into the acinar cells in response to acute pancreatitis behaves like all the other secretory proteins with the exception that it also accumulates in a new fibrillous cellular structure also found in the acinar lumen [1].
• Apoptosis in the androgen-sensitive Dunning R3327 PAP prostatic adenocarcinoma was studied during the post castration period of 14 days and compared with the ventral prostate [2].
• Prostatic acid phosphatase (PAP) is uniquely expressed in prostatic tissue and prostate cancer [3].
• In contrast, immunization with recombinant vaccinia expressing human PAP, but not rat PAP, generates a CTL response and tissue-specific prostatitis in the absence of detectable PAP-specific Abs [3].
• These findings suggest that a cellular immune response to PAP, rather than Abs, mediates destructive autoimmune prostatitis [3].

High impact information on Pdap1

• Its expression is induced by TNF-alpha, and cells overexpressing PAP I show significantly less apoptosis on exposure to TNF-alpha [4].
• The aim of this study was to examine intracellular localization of PAP and amylase in healthy rat pancreas and pancreatitis pancreas to ascertain PAP transport from the rough endoplasmic reticulum to the zymogen granules into the acinar lumen [1].
• PAP is almost absent from normal acinar cells; after acute pancreatitis, it appears in rough endoplasmic reticulum, it is strongly present in normal and abnormal zymogen granules, and it remains an important component of the fibrous material [1].
• BACKGROUND & AIMS: Pancreatitis-associated protein (PAP), which is overexpressed in pancreatic acinar cells, appears in pancreatic juice and serum after acute pancreatitis [1].
• A PAP inhibitor, propranolol, inhibited DG production with a reciprocal increase of PA, implying that PLD played a role in the formation of not only PA but DG [5].

Chemical compound and disease context of Pdap1

• Rats transplanted with the androgen-sensitive Dunning R3327 PAP prostatic adenocarcinoma were castrated and treated with either estrogen or vehicle alone for short periods (4 hr, 12 hr, 24 hr) and for 6 weeks [6].
• The putative serotonin (5-HT)1A agonist 1-[2-(4-aminophenyl)ethyl]-4-(3-trifluormethylphenyl) piperazine (LY165163, PAPP) induces hyperphagia and hypothermia in rats, but unlike other 5-HT agonists, does not induce 5-HT stereotypy even at high doses (10 mg/kg sc) [7].
• In addition, the fMLP-induced lung weight gain of 9 +/- 7 g in the controls was prevented by pretreatment with PAP after 150 min in either concentration [8].
• Treatment with PAP alone in either concentration did not induce any changes in mean pulmonary artery pressure, weight gain, or thromboxane A2 release [8].
• A cell-by-cell analysis of the magnocellular elements in hypothalami of fifty Long-Evans (normal) and Brattleboro (diabetes insipidus) rats was done using the unlabeled antibody enzyme technique (PAP) with primary antisera directed against oxytocin (OXY), vasopressin (ADH), and the neurophysins [9].

Biological context of Pdap1

• The protein copurified with platelet-derived growth factor (PDGF)-A and was therefore termed PDGF-associated protein (PAP). cDNAs corresponding to the protein were characterized from both rat and human cDNA libraries [10].
• Antiapoptotic mechanisms are mediated by NF-kappaB and MAP kinases, and PAP I is one of the effectors of apoptosis inhibition [4].
• It is suggested that one initial event during the androgen-independent prostatic tumor regrowth in the PAP relapse model might be a reduction of the number of tumor cells being depleted by apoptosis, rather than an increase of cell proliferation rate [11].
• We have previously demonstrated that serum factors from rats with acute pancreatitis, but not from healthy rats, could induce endogenous PAP I gene expression in the acinar cell line AR-42J (Dusetti, N., Mallo, G., Dagorn, J.-C., Iovanna, J. L. (1994) Biochem. Biophys. Res. Commun. 204, 238-243) [12].
• In contrast, we found phosphorylation and nuclear translocation of STAT3 and induction of suppressor of cytokine signaling 3 in response to PAP I exposure [13].

Anatomical context of Pdap1

• Important functional similarities to the anti-inflammatory cytokine IL-10 suggest that PAP I could play a role similar to that of IL-10 in epithelial cells [13].
• Lectin binding was detected by polyclonal antibodies using PAP staining to the surface and the parietal cell region of the stomach, the brush border epithelium of the small intestine and to the surface membrane of the caecum and colon [14].
• Design of PAP-1, a selective small molecule Kv1.3 blocker, for the suppression of effector memory T cells in autoimmune diseases [15].
• Significant increases in P-selectin expression, neutrophil infiltration, and oxidative stress revealed that PAP treatment induced lung inflammation in rats and exacerbated inflammation in animals with pancreatitis [16].
• Interestingly, PAPP-A expression in isolated CGCs was also strongly induced by FSH, and the induction was inhibited by added oocytes [17].

Associations of Pdap1 with chemical compounds

• The relapsed, androgen-insensitive PAP tumor shows a dedifferentiated morphology [11].
• PLD hydrolyzes phosphatidylcholine to choline and phosphatidic acid (PA), which is further metabolized to diacylglycerol (DG) by PA phosphohydrolase (PAP) [5].
• ATPDA was a time-dependent irreversible inhibitor of the recombinant AST IV, and this inhibition was prevented by including either PAPS or adenosine 3',5'-diphosphate (PAP) in the incubation of AST IV with ATPDA [18].
• IL-6 and dexamethasone together induced a marked stimulation of PAP I gene transcription, and this effect was slightly attenuated by IL-1 [12].
• Tumor necrosis factor alpha induced an increase in PAP I mRNA expression, and interferon gamma caused an even greater increase in PAP I mRNA level [12].

Regulatory relationships of Pdap1

• The TGFbeta effect on PAP-1 was additive to stimulation induced by dexamethasone but not by glucagon and it reversed the inhibition by insulin [19].

Other interactions of Pdap1

• Of the cDNAs, the p112 regulatory subunit of the 26S proteasome, a PDGF-associated protein and the glia-derived protease nexin PN-1 could be identified [20].
• Epidermal growth factor had no effect on PAP-1 activity [19].

Analytical, diagnostic and therapeutic context of Pdap1

• Pancreata prepared for light and electron microscopy were used for amylase and PAP detection with specific antibodies [1].
• Thus, xenogeneic forms of PAP are a new tool for the induction of prostate-specific immunity and may prove useful for the immunotherapy of prostate cancer [3].
• Levels of reg I/PSP and reg III/PAP were estimated by enzyme-linked immunosorbent assay [21].
• PAP-1 and several of its derivatives therefore constitute excellent new tools to further explore Kv1.3 as a target for immunosuppression and could potentially be developed into orally available immunomodulators [15].
• By in situ hybridization, ovary PAPP-A mRNA was markedly increased by pregnant mare serum gonadotropin treatment, and the message was localized to the membrana GCs but not cumulus GCs (CGCs) of dominant follicles [17].

References