Disease relevance of PLAA

• Two YACs contained both PLAA and D9S259, a marker present in a second more proximal minimal deleted region observed in cutaneous melanoma and squamous cell lung carcinoma [1].
• AIMS: The purpose of this investigation was to discover if PLAP values might be increased in the inflamed intestinal tissue of patients with IBD and in intestinal tissue of mice with colitis [2].
• Phospholipase A2 activating protein and idiopathic inflammatory bowel disease [2].
• To explore the potential mechanisms of action of PLAP that extend beyond its effects on eicosanoid synthesis, we examined its effects on the release of human neutrophil lysosomal enzymes and superoxide, and on RBC hemolysis [3].
• CONCLUSIONS.: The present study documents for the first time expression of PLA(2) isoforms, sPLA(2)R and PLAP in ovarian carcinoma [4].

High impact information on PLAA

• Sequence similarity of phospholipase A2 activating protein and the G protein beta-subunits: a new concept of effector protein activation in signal transduction [5]?
• The steady-state levels of PLAP mRNA are induced in smooth muscle and endothelial cells following treatment with leukotriene D4 [6].
• The role of PLAA in eicosanoid formation in macrophages was confirmed by the use of an antisense plaa oligonucleotide [7].
• PLAP can also be found in high concentrations in synovial fluid from patients with rheumatoid arthritis, and injection of PLAP into animal joints results in an inflammatory, rheumatoid-like lesion [8].
• IL-1 increases phospholipase A2 activity, expression of phospholipase A2-activating protein, and release of linoleic acid from the murine T helper cell line EL-4 [9].

Chemical compound and disease context of PLAA

• CONCLUSIONS: As PLAP values were increased in the intestinal mucosa of IBD patients and mice with colitis, as well as in LPS treated cultured HT-29 cells, a role was postulated for PLAP in increasing PLA2 activity, which leads to the increased synthesis of eicosanoids in intestinal tissues of patients with these inflammatory diseases [2].
• Concentrations of PLAP that induced these responses did not induce cellular toxicity as determined by light and electron microscopy, lactic dehydrogenase release, trypan blue dye exclusion, and RBC hemolysis [3].

Biological context of PLAA

• Fluorescence in situ hybridization (FISH) mapping placed PLAA on chromosome 9p21, a region frequently deleted in various cancers [1].
• Despite PLAP's important role in mediating several cellular responses and its localisation to the chromosome 9p21 region deleted in CMM, it is unlikely that point mutations or deletions in the coding region of PLAP are responsible for the initiation or progression of CMM [10].
• SSCP analysis of the coding region of PLAP revealed no variants in the studied samples, but one of six CMM samples analysed by RT-PCR showed specific inactivation of PLAP [10].
• A phospholipase A2-activating protein (PLAP) cDNA was cloned and sequenced from a human monocyte cDNA library, and expressed as a histidine-tagged fusion protein [11].
• We also examined the effects of PLAP on neutrophil aggregation and chemotaxis [3].

Anatomical context of PLAA

• RESULTS: PLAP antigen was localised predominantly within monocytes and granulocytes in intestinal tissue sections from IBD patients, and additional deposition of extracellular PLAP antigen was associated with blood vessels and oedema fluid in the inflamed tissues [2].
• These data were supported by northern analysis which showed that PLAP mRNA was increased in the colons of DSS treated mice and cultured HT-29 cells exposed to LPS [2].
• In contrast, tissue sections from normal human intestine were devoid of PLAP reactive antigen, except for some weak cytoplasmic reaction of luminal intestinal epithelial cells [2].
• The stroma of the lamina propria of the colonic mucosa from the DSS treated mice reacted intensely with antibodies to PLAP synthetic peptides, while no reaction was observed with control mouse colons [2].
• Low concentrations of melittin and PLAP were observed to inhibit sPLA2-triggered release of fatty acids from erythrocyte membranes [12].

Associations of PLAA with chemical compounds

• Anti-sense plap oligonucleotide blocked cholera toxin-induced release of 3H-labeled arachidonic acid from cells, indicating a potential role for PLAP in regulating phospholipase A2 activity [11].
• Prostaglandin levels in stimulated macrophages are controlled by phospholipase A2-activating protein and by activation of phospholipase C and D [7].
• Monosodium urate crystals stimulate phospholipase A2 enzyme activities and the synthesis of a phospholipase A2-activating protein [13].
• We determined the k(cat) and K(m), of the PLAP S, F, and D allozymes using the non-physiological substrate p-nitrophenylphosphate at an optimal pH (9.8) as well as two physiological substrates, i.e., pyridoxal-5-phosphate and inorganic pyrophosphate at physiological pH (7.5) [14].
• At least one effector of the G protein is phospholipase A2 as demonstrated by the observation that the phospholipase A2 activating protein peptide efficiently blocks peroxisomal motility, and that the effect of mastoparan and AlF4- is largely abolished by various phospholipase A2 inhibitors [15].

Other interactions of PLAA

• A comprehensive mapping strategy was employed to define further the chromosomal localization of PLAA relative to CDKN2A within the 9p21 locus [1].
• Double-color fiber FISH mapping confirmed the location of PLAA centromeric to D9S171 and CDKN2A/CDKN2B [1].

Analytical, diagnostic and therapeutic context of PLAA

• Northern blot analysis with a murine [32P] labelled plap cDNA probe was performed on RNA extracted from the colons of mice fed dextran sulphate sodium (DSS) and cultured HT-29 cells exposed to lipopolysaccharide (LPS) [2].
• METHODS: Immunocytochemistry with affinity purified antibodies to PLAP synthetic peptides was used to locate PLAP antigen in sections of intestinal biopsy specimens from IBD patients compared with that of normal intestinal tissue [2].
• The DNA-deduced aa sequence of human PLAP was 80,826 Da; however, SDS-PAGE analysis revealed a 72-74 kDa protein which matched the size of native PLAP from human monocytes [11].
• With enzyme-linked immunosorbent assays, we found more PLAP in synovial fluid specimens from patients with rheumatoid arthritis compared with samples from patients with other inflammatory arthropathies as well as osteoarthritis, a noninflammatory arthropathy [16].
• A single nucleotide primer extension (SNuPE) assay was developed using PCR primers that enable the amplification of a 1.9 kb PLAP fragment [14].

References