Disease relevance of PDAP1

• Antiproliferative effect of trapidil on PDGF-associated growth of human glioma cell lines in vitro [1].
• Both the proband and her affected brother had RP, PAP, mild mental retardation, morbid obesity (BMI >50 and 37, respectively), lobulated kidneys with prominent calyces and diabetes mellitus (diagnosed at ages 33 and 30, respectively) [2].
• The first is a 13-year-old Hispanic girl with severe RP, PAP, mental retardation and obesity (BMI >40) [2].
• Of two patients tested, the PAP RAID scintiscans located the primary or recurrent prostatic cancers in both and showed no disease in the lungs of the patient shown subsequently to have lung cancer [3].
• The antibody was found to be present in all specimens of bronchoalveolar lavage fluid obtained from 11 I-PAP patients but not in samples from 2 secondary PAP patients, 53 normal subjects, and 14 patients with other lung diseases [4].

Psychiatry related information on PDAP1

• The PDAPP transgenic mouse, which overexpresses mutant human APP (in which the amino acid at position 717 is phenylalanine instead of the normal valine), progressively develops many of the neuropathological hallmarks of Alzheimer's disease in an age- and brain-region-dependent manner [5].
• Age-independent and age-related deficits in visuospatial learning, sleep-wake states, thermoregulation and motor activity in PDAPP mice [6].
• Aged PDAPP mice also showed an increase in the amount of time spent in W and a reduction in REM sleep during the dark period [6].
• The measurement of transmural values allowed a reliable assessment of PAP changes occurring during apneas, and different degrees of such changes shown by different patients may be related to a host of factors relevant to wakefulness and sleep, including individual responsivity to hypoxic stimulus [7].
• This review presents the possible involvement of 3'(2')-phosphoadenosine-5'-phosphate (PAP) phosphatase in the etiology of bipolar disorder and the mechanism of action of Li [8].

High impact information on PDAP1

• Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse [5].
• Monospecific rabbit antiserums to PAPP-A, PAPP-C and hCS all stained the trophoblast cytoplasm equivalently in a continuous layer, usggesting that the same trophoblast cells synthesize all three pregnancy proteins [9].
• We first measured hippocampal acetylcholine (ACh) release in young, freely moving PDAPP mice, a well-characterized transgenic mouse model of AD, and found marked A beta-dependent alterations in both basal and evoked ACh release compared with WT controls [10].
• Pulmonary alveolar proteinosis (PAP) is a heterogeneous disorder of genetic or acquired etiologies [11].
• Overall, the apparent order of prognostic reliability for disease progression was found to be PA greater than PAP greater than BAP greater than AcP greater than TAP [12].

Chemical compound and disease context of PDAP1

• We used this SCID mouse model of human pre-B ALL to evaluate and compare, in a total of 434 SCID mice, the antileukemic efficacy of B43 (anti-CD19)-pokeweed antiviral protein (PAP) immunotoxin and cyclophosphamide (CPA) as individual reagents and as combined immunochemotherapeutic regimens [13].
• HIP/PAP transgenic mice were protected against acetaminophen-induced acute liver failure and were stimulated to regenerate post-hepatectomy [14].
• Estrogen therapy fails to alter amyloid deposition in the PDAPP model of Alzheimer's disease [15].
• While neither low nor high doses of DHAS and PAP exerted any significant influence on the incidence of ductal lesions including carcinomas, the high dose of DHAS (350 mg/kg body wt) and a both low (90 mg/kg) and high (180 mg/kg) doses of PAP reduced the mean numbers of pancreatic ductal adenocarcinomas [16].
• We found some correlation between CPK-BB and androgen cytosolic receptors as well as between PAP content and androgen cytosolic receptors in patients with benign hyperplasia [17].

Biological context of PDAP1

• PAP-2 contains two clip domains at its amino terminus and a catalytic domain at its carboxyl terminus, whereas PAP-1 has only one clip domain [18].
• Pap1 and Pap2 are more similar to each other (84% amino acid sequence identity) than to Pap3 (46% and 44%, respectively) in the encoded mature proteins [19].
• Here we showed that in cultured human vascular smooth muscle cells (SMC), the PKC stimulator phorbol 12-myristate 13-acetate (PMA) inhibited [(3)H]thymidine incorporation in response to the growth factor PDGF associated with downregulation of PDGFbeta (but not alpha) receptors, which was recovered to normal level after PKC was depleted [20].
• The observed results are in agreement with the concentration-dependent kinetics of hPAP reactivation, assuming that the reconstitution of the active enzyme requires the association of subunits in dimeric form [21].
• In an effort to understand the transcriptional regulation, we isolated a genomic clone of the PAP-1 gene, determined its nucleotide sequence, and elucidated its exon-intron organization [22].

Anatomical context of PDAP1

• Treating M. sexta fat body culture with 20-hydroxyecdysone reduced the PAP-1 mRNA level [22].
• Reverse transcription-polymerase chain reaction showed that PAP-1 was constitutively expressed in fat body, trachea, and nerve tissue of the fifth instar larvae [22].
• We previously isolated PAP-1 from integument and PAP-2 from hemolymph of the tobacco hornworm, Manduca sexta [23].
• Although Kv1.3 inhibitors [ShK(L5)-amide (SL5) and PAP1] do not prevent immunological synapse formation, they suppress Ca(2+)-signaling, cytokine production, and proliferation of autoantigen-specific T(EM) cells at pharmacologically relevant concentrations while sparing other classes of T cells [24].
• The present study represents the first complete 3D reconstruction of A beta in the hippocampus and entorhinal cortex of PDAPP transgenic mice [25].

Associations of PDAP1 with chemical compounds

• Manduca sexta PAP-1, the final component of a serine proteinase cascade, cleaves proPO to generate active PO [22].
• Human prostatic acid phosphatase (hPAP) [EC 3.1.3.2], a homodimer of ca. 50 kDa subunit molecular weight, shows reversible denaturation in 6 M urea at pH 2 [21].
• Treatment of PDAPP mice with the anti-A beta antibody m266 rapidly and completely restored hippocampal ACh release and high-affinity choline uptake while greatly reducing impaired habituation learning that is characteristic of these mice [10].
• In contrast, correlations were noted between PS-positive erythrocytes and F1.2 (P <.0002), D-dimer (P <.000002), and PAP (P <.01) [26].
• Estradiol reduced the levels of PAP in sera from untreated male mice regardless of the tumor weight [27].

Other interactions of PDAP1

• It is also the likely precursor of high molecular mass PDGF-like or PDGF-associated proteins secreted by these cells [28].
• Using M. sexta as a model system, we found that Vn50 efficiently down-regulated proPO activation mediated by M. sexta PAP-1, SPH-1, and SPH-2 [29].
• The PDAPP transgenic mouse, which overexpresses human amyloid precursor protein (APP717V-->F), has been shown to develop much of the pathology associated with Alzheimer disease [30].
• Immunizing transgenic PDAPP mice, which overexpress mutant APP and develop beta-amyloid deposition resembling plaques in Alzheimer's disease (AD), results in a decrease of amyloid burden when compared with non-treated transgenic animals [31].
• Using immunohistochemistry we show that LRP was present only on cored, apoE-containing senile plaques, in both PDAPP transgenic mice and human AD brains [32].

Analytical, diagnostic and therapeutic context of PDAP1

• The renaturation reaction of hPAP was examined using spectral analysis (circular dichroism and fluorometry), fast size-exclusion chromatography and proteolysis by trypsin [21].
• Southern blot analysis suggested that the M. sexta genome contains a single copy of PAP-1 gene [22].
• Frozen sections of human placenta were examined for the presence of four human pregnancy proteins, pregnancy-associated plasma proteins A and C (PAPP-A and PAPP-C), human chorionic somatomammotropin (hCS), and pregnancy zone protein (PZP), by the indirect immunofluorescence technique [9].
• The lung tumor nodules showing anti-PAP IgG accretion were assumed to be of prostatic cancer origin, since one of the original tumors removed from this patient's other lung a year earlier stained for PAP by immunohistochemistry [3].
• Radioimmunodetection (RAID) of prostatic cancer is done by injecting 131I-labeled rabbit antibody IgG against prostatic acid phosphatase (PAP) and performing total-body photoscans with a gamma scintillation camera [3].

References