Disease relevance of Pap

• p8 improves pancreatic response to acute pancreatitis by enhancing the expression of the anti-inflammatory protein pancreatitis-associated protein I [1].
• After 3 days' hypoxia pancreatitis-associated protein mRNA levels were again undetectable [2].
• 3. In the pancreas the level of pancreatitis-associated protein mRNA was also increased by alcohol and iron overload, but not by paracetamol [2].
• Structural organization and chromosomal localization of a human gene (HIP/PAP) encoding a C-type lectin overexpressed in primary liver cancer [3].
• Pancreatitis-associated pulmonary inflammation was independent of the integrity of the vagus nerve and nicotinic receptors [4].

High impact information on Pap

• Recent functional and molecular evidence indicate that the predominant potassium conductance of the kidney medullary cell line GRB-PAP1 is composed of Shaker-like potassium channels [5].
• The role of COX in acute pancreatitis and pancreatitis-associated lung injury is not known [6].
• Cyclooxygenase-2 gene disruption attenuates the severity of acute pancreatitis and pancreatitis-associated lung injury [6].
• Cd40 ligand-deficient mice are protected against cerulein-induced acute pancreatitis and pancreatitis-associated lung injury [7].
• Neither pancreatitis nor pancreatitis-associated lung injury are completely prevented by ICAM-1 deficiency, neutrophil depletion, or combined ICAM-1 deficiency plus neutrophil depletion [8].

Chemical compound and disease context of Pap

• 5. In the ileum long-term (4 weeks) dietary iron deficiency reduced pancreatitis-associated protein mRNA levels compared with control fed mice, whereas parenteral iron overload increased pancreatitis-associated protein mRNA levels [2].
• Role of substance P and the neurokinin 1 receptor in acute pancreatitis and pancreatitis-associated lung injury [9].
• Unlike classical NESs such as the human immunodeficiency virus Rev NES, the Pap1 NES lost the function upon treatment with oxidants such as diethyl maleate [10].
• OBJECTIVE: The objective of this study was to demonstrate that islet neogenesis-associated protein (INGAP) peptide, a pentadecapeptide containing the biologically active portion of native INGAP, increases functional beta-cell mass in normal animals and can be used therapeutically to reverse hyperglycemia in streptozotocin-induced diabetes [11].
• In both strains of genetically altered mice, the severity of pancreatitis and pancreatitis-associated lung injury was greater than that noted in the comparison wild-type strains of C5aR- and C5-sufficient animals [12].

Biological context of Pap

• 6. The data presented suggest regulation of pancreatitis-associated protein gene expression by both oxygen tension and iron status [2].
• We provide evidence for the localization of HIP/PAP on chromosome 2, suggesting previous duplication of HIP/PAP and the related reg I alpha and reg I beta genes from the same ancestral gene [3].
• Furthermore, the analysis of HIP/PAP gene indicates that the HIP/PAP CRD is encoded by four exons, a pattern shared with all members of this group of proteins [3].
• The nucleotide sequences of cDNAs encoding human and mouse homologous for rat pancreatitis-associated protein (PAP) (J. Iovanna et al. (1991) J. Biol. Chem. 266, 24664-24669) were determined [13].
• Similarly, pancreatitis-associated lung injury, as characterized by intrapulmonary sequestration of neutrophils and increased pulmonary microvascular permeability, was reduced in NK1R-/- animals [9].

Anatomical context of Pap

• In the ileum pancreatitis-associated protein mRNA levels were increased 7 to 15-fold after 6 h hypoxia, reaching peak levels by 24 h [2].
• 1. In the present study we have examined the expression of pancreatitis-associated protein mRNA in mouse pancreas and small intestine and determined the effect of a number of factors on the steady-state level of the RNA [2].
• 4. In the small intestine expression of pancreatitis-associated protein mRNA was higher in normal ileum than in duodenum [2].
• The role of intercellular adhesion molecule 1 and neutrophils in acute pancreatitis and pancreatitis-associated lung injury [8].
• Administration of INGAP peptide to diabetic mice reversed the diabetic state in all animals, and this was associated with increased expression of PDX-1 in duct cells and islet cell neogenesis with a reduction of insulitis in the new islets [11].

Associations of Pap with chemical compounds

• The oxidative stress response is conserved through evolution, as green fluorescent protein-fused proteins bearing the Pap1 NES expressed in mammalian cells responded to diethyl maleate [10].
• In support of this view, BEL-induced apoptosis is accompanied by a very strong inhibition of PAP-1-regulated events, such as incorporation of [3H]choline into phospholipids and de novo incorporation of [3H]arachidonic acid into triacylglycerol [14].
• Deletion of the C-terminal cysteine-rich domain (CRD) resulted in nuclear accumulation of Pap1, while a glutathione S-transferase-green fluorescent protein-CRD fusion protein was localized in the cytoplasm in a Crm1-dependent manner [10].
• However, propranolol, a PAP-1 inhibitor, is able to reproduce these effects, suggesting that it is the inhibition of PAP-1 and not of iPLA2 that is involved in BEL-induced cell death [14].
• Blood glucose and insulin levels were measured, and a histologic and morphometric analysis of the pancreas was performed to determine the effect of INGAP peptide on the endocrine pancreas [11].

Regulatory relationships of Pap

• RESULTS: Islet cell neogenesis was stimulated in INGAP-treated hamsters by 10 days [11].
• Furthermore, pharmacological inhibition of adenylate cyclase with SQ22,536 or of protein kinase A with H89 or KT5720 significantly reduced the neurite-promoting effects of INGAP peptide [15].
• BACKGROUND: Select pancreatic enzymes, primarily elastase, precipitate pulmonary injury similar to pancreatitis-associated adult respiratory distress syndrome and stimulate leukocyte cytokine production in vitro via nuclear factor kappa B (NF-kappaB) activation [16].

Other interactions of Pap

• 2. The normally low level of pancreatitis-associated protein mRNA in pancreas increased severalfold after 6 h of hypoxia, reaching peak levels (approximately 10-fold greater than normal) after 24 h hypoxia [2].
• Deletion of PPT-A almost completely protected against acute pancreatitis-associated lung injury, with a partial protection against local pancreatic damage [17].
• We have earlier shown that treatment with a neutralizing antibody against CINC, a CXC chemokine, protects rats against acute pancreatitis-associated lung injury [18].
• Neutral endopeptidase determines the severity of pancreatitis-associated lung injury [19].
• We found that the severity of acute pancreatitis and pancreatitis-associated lung injury was significantly attenuated in mice lacking PARP-1, but not PARP-2, compared with WT mice [20].

Analytical, diagnostic and therapeutic context of Pap

• RESULTS: Administration of caerulein and LPS induced an increase in serum amylase and IL-6 levels, severe acute pancreatitis, pancreatitis-associated lung injury, and phosphorylation of signal transducer and activator of transcription (STAT) 3 in the pancreas [21].
• Intrapancreatic expression of the pancreatitis-associated protein (PAP), a marker of pancreatic inflammation, was monitored by automated immunohistochemistry using specific antibodies [22].
• CONCLUSION: A completely noninvasive animal model of acute pancreatitis-associated lung injury was used to show that neutrophils, activated by pancreatitis, play a key role in mediating pancreatitis-associated lung injury [23].
• In a preclinical mouse model the plant ribosome-inactivating proteins (RIPs) pokeweed antiviral proteins PAP-1, and PAP-S and ricin A-chain (RTA) induced a pathological elevation of serum concentrations of glutamate pyruvate transaminase (GPT) and blood urea nitrogen (BUN) and had a significant immunosuppressive effect on B- and T-lymphocytes [24].

References