Disease relevance of PR39

• Adenoviral PR39 improves blood flow and myocardial function in a pig model of chronic myocardial ischemia by enhancing collateral formation [1].
• PR-39 is a porcine 39-aa peptide antibiotic composed of 49% proline and 24% arginine, with an activity against Gram-negative bacteria comparable to that of tetracycline [2].
• Mechanisms of action on Escherichia coli of cecropin P1 and PR-39, two antibacterial peptides from pig intestine [3].
• This truncated form of PR-39 potentiated neutrophil phagocytosis of Salmonella choleraesuis and decreased the level of S. typhimurium invasion into intestinal epithelial cells [4].
• Furthermore, PR-39 did not induce neutrophil chemotaxis in the absence of extracellular Ca2+, and pertussis toxin inhibited both neutrophil chemotaxis and Ca2+ mobilization [5].

High impact information on PR39

• Here we show that a macrophage-derived peptide, PR39, inhibited the ubiquitin-proteasome-dependent degradation of hypoxia-inducible factor-1alpha protein, resulting in accelerated formation of vascular structures in vitro and increased myocardial vasculature in mice [6].
• For the latter, coronary flow studies demonstrated that PR39-induced angiogenesis resulted in the production of functional blood vessels [6].
• Lentiviral delivery of PR-39 enhanced killing of GAS by human keratinocytes [7].
• PR-39, a proline-rich antibacterial peptide that inhibits phagocyte NADPH oxidase activity by binding to Src homology 3 domains of p47 phox [8].
• We show here that an endogenous proline-arginine (PR)-rich antibacterial peptide, PR-39, inhibits NADPH oxidase activity by blocking assembly of this enzyme through interactions with Src homology 3 domains of a cytosolic component [8].

Biological context of PR39

• PR39 was mapped to pig chromosome 13 by linkage and in situ hybridization mapping [2].
• Genomic hybridizations revealed a fairly high level of restriction fragment length polymorphism and indicated that there are at least two copies of the PR39 gene in the pig genome [2].
• PR39 enhances hypoxia-inducible factor-1alpha (HIF-1alpha)-dependent gene expression by selectively inhibiting proteasome degradation of this transcription factor [1].
• Exons 2 and 3 contain only cathelin information, while exon 4 codes for the four C-terminal cathelin residues and the mature PR-39 peptide extended by three residues [2].
• The open reading frame of the clone showed that PR-39 is made as 173-aa precursor whose proregion belongs to the cathelin family [2].

Anatomical context of PR39

• In this study, we investigated the efficacy and mechanism of PR39, a gene capable of activating VEGF and fibroblast growth factor (FGF)-2-dependent pathways [1].
• PR39 is an angiogenic peptide that improves perfusion and function of ischemic myocardium, at least in part, through collateral formation [1].
• PR-39 was originally isolated from pig small intestine, but subsequent cDNA cloning showed that the gene is expressed in the bone marrow [2].
• Cecropin P1 and PR-39 are two antibacterial peptides isolated from the upper part of the small intestine of the pig [3].
• Peripheral blood neutrophils from young pigs expressed PR-39 and protegrin mRNA, which were not detectable at 42 days of age [9].

Associations of PR39 with chemical compounds

• Its effects involve both a polybasic amino-terminal segment and a proline-rich core region of PR-39 that binds to the p47phox Src homology 3 domains and, thereby, inhibits interaction with the small subunit of cytochrome b558, p22phox [8].
• The proline-arginine (PR) -rich antibacterial peptide, PR-39, kills bacteria by a non-pore-forming mechanism [5].
• We report on the synthesis of a functional antibacterial domain of PR-39, the first 26 amino acid residues of the NH2 terminus [4].
• Exon IV specified the final few cathelin residues, including its conserved C-terminal valine, followed by the mature PR-39 peptide or a PF-2 precursor [10].
• PR-39 induced a calcein release from large unilamellar vesicles, which is dependent upon the peptide concentration and upon the presence of negatively charged lipid (glycerophosphoglycerol) in the membrane [11].

Regulatory relationships of PR39

• In addition, PR39 also stimulates expression of the FGF receptors (FGFR)-1 and syndecan-4 [1].

Other interactions of PR39

• The dual mechanism, i.e., stimulation of HIF-1alpha and FGF receptor expression, likely accounts for the functional benefits of PR39 [1].
• In 10 mM sodium phosphate with 125 mM NaCl, the combinations of sublethal concentrations of PBD-1 and the porcine neutrophil peptide PG-3, PR-39, or PR-26 showed synergistic activity against E. coli or the multidrug-resistant S. typhimurium DT104 [12].
• Chemoattractant properties of PR-39, a neutrophil antibacterial peptide [5].
• Spleen antibacterial peptides: high levels of PR-39 and presence of two forms of NK-lysin [13].

Analytical, diagnostic and therapeutic context of PR39

• Intending to isolate a clone for a human counterpart to PR-39, we synthesized a PCR probe derived from the PR-39 gene [14].
• Intracellular Ca2+ fluxes in response to PR-39 were monitored by flow cytometry and showed a transient increase that peaked at approximately 40 s and approached basal values by 4 min [5].
• C-terminal ladder sequence analysis of a bioactive peptide with matrix-assisted laser desorption/ionization mass spectrometry after digestion with carboxypeptidases P and Y showed that it is identical to the antibacterial proline/arginine-rich intestinal peptide PR-39 [13].
• Circular dichroism and Fourier-transform infrared spectroscopy have been used to investigate the secondary structure of PR-39 in the absence or presence of lipids [11].
• To investigate the involvement of PR-39 in a Salmonella choleraesuis infection, a PR-39 enzyme immunoassay was developed [15].

References