Disease relevance of Pam

• Extracts of the EHS tumor, which produces an extracellular matrix containing basement membrane components, were tested for their ability to promote attachment to cycloheximide-treated PAM 212 cells [1].
• In vitro treatment of a murine keratinocyte cell line PAM 212 with PUVA caused the release of soluble factors that, when mixed with K1735 melanoma cells prior to injection, stimulated their outgrowth in vivo [2].
• We found previously that variants of murine squamous cell carcinoma PAM 212 which grow and metastasize more rapidly in vivo constitutively express increased levels of murine GRO-alpha, designated mGRO-alpha, or KC [3].
• PAM cell assay as a tests for multiple-sclerosis associated agent [4].
• Lysates prepared from cultures 16 passages after treatment with scrapie caused the decrease when applied to fresh PAM cultures [5].

High impact information on Pam

• Role of laminin in the attachment of PAM 212 (epithelial) cells to basement membrane collagen [1].
• Prostacyclin formation by PAM was not observed [6].
• Mouse resident pulmonary macrophages were subdivided into alveolar (PAM) and interstitial (PTM) populations on the basis of accessibility to pulmonary lavage, and zymosan-induced arachidonic acid (20:4) metabolism was examined in both populations labeled with [3H]20:4 [6].
• In contrast, PAM produced leukotrienes D and E in addition to leukotriene C, prostaglandin E2, thromboxane A2, and hydroxyeicosatetraenoic acids [6].
• Using a cDNA probe directed against NGF, we demonstrated the presence of a 1.3-kb NGF mRNA in both PAM 212 and BALB/c keratinocytes [7].

Chemical compound and disease context of Pam

• The AtT20 corticotropic pituitary tumor cell line also contains PAM and a potential site for COOH-terminal alpha-amidation of the pro-ACTH/endorphin-derived hinge peptide and was, thus, used for the study of cellular ascorbate transport [8].
• Mouse neuroblastoma N(18)TG(2) cells are an excellent model system for the study of oleamide biosynthesis because these cells convert [(14)C]-oleic acid to [(14)C]-oleamide and express PAM in a regulated fashion [9].
• HI-6, but neither toxogonin nor PAM Cl, antagonized sarin-induced hypothermia and reactivated brain acetylcholinesterase, in particular hypothalamic acetylcholinesterase [10].
• Effects of the novel alphav integrin antagonist SM256 and cis-platinum on growth of murine squamous cell carcinoma PAM LY8 [11].
• Lethal photosensitization by endogenous porphyrins of PAM cells--modification by desferrioxamine [12].

Biological context of Pam

• Localization of the peptidylglycine alpha-amidating monooxygenase gene (Pam) introduces a region of homology between human chromosome 5q and mouse chromosome 1 [13].
• No peptide amidation activity was detected in PAM mutant embryos, and there was no moderation of the AM-like phenotype that could be expected if any alternative peptide amidation mechanism exists in the mouse [14].
• To determine the function of PAM during mouse embryogenesis, we produced a null mutant of the PAM gene [14].
• In 12-day-old (P12) mouse pups derived from dams that began Cu deficiency on day 7 of gestation, there was a parallel reduction in brain PAM activity and protein of 40-50% [15].
• The exon following the PAL domain encodes the trans-membrane domain of PAM; alternative splicing at this site produces integral membrane or soluble PAM proteins [16].

Anatomical context of Pam

• These defects include thinning of the aorta and carotid arteries and are very similar to those of the recently characterized adrenomedullin (AM) gene KO despite the presence of elevated immunoreactive AM in PAM KO embryos [14].
• In adult mouse lung, immunostaining for PAM was located in Clara cells, which constitute most of the epithelial cells of the mouse bronchial/bronchiolar tree [17].
• Smooth muscle of airways and blood vessels, and some parenchymal cells, probably macrophages, also showed PAM immunoreactivity [17].
• No reduction in Cu- rat midbrain PAM protein was detected although PAM activity was reduced 40% [15].
• Short-term DETC lines were 35S-labeled and tested for migration toward Pam 212 keratinocyte culture supernatants using a modified Boyden chamber method; cell movement from upper chambers toward test samples in lower chambers was traced by counting radioactivity [18].

Associations of Pam with chemical compounds

• Chemotactic activities were 1) produced by Pam 212 cells even in the absence of serum; 2) greater than 12 kD in size; 3) heat and pH labile; 4) trypsin sensitive; and 5) precipitated by 60-100% ammonium sulfate [18].
• Preincubation of the PAM 212 cells with cycloheximide prevented attachment [1].
• The bifunctional PAM protein contains an NH2-terminal monooxygenase (PHM) domain followed by a lyase (PAL) domain and a transmembrane domain [19].
• It was equally effective in inhibiting the growth of the murine L1210 line and of a subline (L1210/PAM) resistant to nitrogen mustards, whereas distamycin A was virtually inactive [20].
• Peptidylglycine alpha-amidating monooxygenase is a copper- and ascorbate-dependent enzyme that converts peptides with COOH-terminal glycine residues into the corresponding alpha-amidated product peptides [21].

Other interactions of Pam

• Menkes protein contributes to the function of peptidylglycine alpha-amidating monooxygenase [22].
• AtT-20 cells synthesize and store endogenous proopiomelanocortin and prohormone convertase 1; AtT-20 cells expressing high levels of integral membrane or soluble peptidylglycine alpha-amidating monooxygenase were generated by stable transfection [23].
• Plasma peptidylglycine alpha-amidating monooxygenase (PAM) and ceruloplasmin are affected by age and copper status in rats and mice [24].

Analytical, diagnostic and therapeutic context of Pam

• Western blots of crude membrane and soluble fractions of transfected cells demonstrated that all PAM proteins were endoproteolytically processed [25].
• Furthermore, immunoprecipitation of cell surface-associated integral membrane PAM demonstrated that very little integral membrane PAM reached the cell surface during early times of chase [26].
• Northern blot analysis (PAM 212 cells) and in situ hybridization (normal keratinocytes) demonstrate expression of M-CSF mRNA [27].
• Transfection and cellular expression of IFNgamma from the bicistronic pGTmCMV.IFN-GFP plasmid were evaluated in PAM 212 keratinocyte culture by ELISA and fluorescence microscopy [28].
• We compared the effect on growth of PAM LY8 of SM256 infusion versus single agent or combination chemotherapy with a maximally tolerated dose of cis-platinum, which is used as a standard chemotherapy for SCC [11].

References