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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our recent published studies suggest that angiotensin II (AII), generated and retained intracellularly, enhances growth of H4-II-E-C3 rat hepatoma cells, an average of 33%. Proliferation conferred by introduction of a plasmid [ Ang(-S)Exp/pSVL ] encoding a signal sequence-depleted angiotensinogen [Ang(-S)Exp] into these cells (which we have shown possess ACE and renin mRNAs) is mediated, at least in part, by enhanced PDGF-A chain mRNA production and protein secretion. The mitogenic effect is inhibited by losartan suggesting that it involves AII interaction with an AT(1)-like receptor. Introduction of anti-AII antibodies into the medium of these transfected cells has no effect upon growth of the cells, suggesting that AII is retained by the cells and that intracellular AII is growth stimulatory. In the present study, we sought to further characterize the intracellular localization and mode of action of Ang(-S)Exp. Consistent with our expectations, we now show that a fusion product of Ang(-S)Exp with green fluorescent protein [Ang(-S)Exp/EGFP], generated from an expression plasmid, is abundant and primarily cytoplasmic. Wild-type angiotensinogen/EGFP, in contrast, is only detectable following a cold-block (which acts to enhance folding-kinetics and slow secretion) and is largely restricted to the secretory pathway. We further show, using semi-quantitative RT/PCR that the long isoform of PDGF mRNA is elevated in Ang(-S)Exp transfected cells and in AII-treated naive cells but not in losartan-treated Ang(-S)Exp transfected cells. We identify C-terminal amidation recognition sites within the long-form protein (that are not present in the short-form) and show that these cells possess PAM (amidating enzyme precursor) and carboxypeptidase E mRNAs (the corresponding proteins of which are sufficient for amidation). Inhibitors of amidation inhibit growth of naive and Ang(-S)Cntr/ pSVL -transfected cells (2.6-fold for phenylbutenoic acid and 3.5-fold for disulfiram treatment) but more profoundly inhibit growth of Ang(-S)Exp/pSVL -transfected cells (6.7-fold for phenylbutenoic acid and 13-fold for disulfiram). In conclusion, these data confirm that signal sequence-depleted Ang(-S)Exp is retained within cells and is largely cytoplasmic. Because C-terminal amidation is absolutely required for full biological potency of a number of peptide hormones (including oxytocin, gastrin and calcitonin), we postulate that growth effects of both intracellular AII and exogenous AII can be conferred by PDGF long-form, possibly through an amidation-dependent mechanism.
J Mol Cell Cardiol 2002 Nov
PMID:Intracellular angiotensin II increases the long isoform of PDGF mRNA in rat hepatoma cells. 1243 51

A novel polyacrylamide superparamagnetic iron oxide nanoparticle platform is described which has been synthetically prepared such that multiple crystals of iron oxide are encapsulated within a single polyacrylamide matrix (PolyAcrylamide Magnetic [PAM] nanoparticles). This formulation provides for an extremely large T2 and T2* relaxivity of between 620 and 1140 sec(-1) mM(-1). Administration of PAM nanoparticles into rats bearing orthotopic 9L gliomas allowed quantitative pharmacokinetic analysis of the uptake of nanoparticles in the vasculature, brain, and glioma. Addition of polyethylene glycol of varying sizes (0.6, 2, and 10 kDa) to the surface of the PAM nanoparticles resulted in an increase in plasma half-life and affected tumor uptake and retention of the nanoparticles as quantified by changes in tissue contrast using MRI. The flexible formulation of these nanoparticles suggests that future modifications could be accomplished allowing for their use as a targeted molecular imaging contrast agent and/or therapeutic platform for multiple indications.
Mol Imaging 2003 Oct
PMID:A novel polyacrylamide magnetic nanoparticle contrast agent for molecular imaging using MRI. 1471 31

Squamous cell carcinoma (SCC) is the most prevalent form of epithelial cancer. SCC results when normal epithelial cells undergo multiple neoplastic changes that culminate in the evolution of an invasive cancer. Retinoids are commonly used as chemopreventive and treatment agents in skin cancer; however, SCC progression is accompanied by a gradual loss of retinoid responsiveness. The synthetic retinoid N-(4-hydroxyphenyl)retinamide (HPR) has shown promising anti-neoplastic activity in a variety of tumor cells, including those that are resistant to all-trans retinoic acid (t-RA). We investigated the effect of HPR on growth and apoptosis of squamous cells at different stages of carcinogenesis. We then determined if retinoic acid receptor (RAR) overexpression affected the outcome of HPR treatment. To model SCC malignant progression, we used a panel of murine keratinocytes representing different stages of squamous cell carcinogenesis. This panel consisted of primary keratinocytes, SP1 and 308 papilloma cell lines, the PAM-212 squamous carcinoma cell line, and the spindle I7 cell line. With the exception of the primary keratinocytes, all cells were unresponsive to t-RA treatment. Pharmacological concentrations of HPR were non-cytotoxic to all keratinocytes tested and HPR sensitivity was stage-dependent, with the papilloma cell lines being the most sensitive, and the spindle cells being the most resistant. Overexpression of RARgamma in SP1 papilloma cells enhanced growth suppression and apoptosis induction by HPR. HPR-induced growth suppression was accompanied by a simultaneous block in the G(1) phase of the cell cycle in RAR-transduced and control SP1 cells and differential regulation of cell cycle and apoptotic mediators.
Mol Carcinog 2004 May
PMID:Stage-specific effect of N-(4-hydroxyphenyl)retinamide on cell growth in squamous cell carcinogenesis. 1510 26

This method describes the use of subtilisin-catalyzed peptide condensation to form a 15-residue glycopeptide from two smaller synthetic peptides. A 12-residue peptide ester is synthesized by solid-phase peptide synthesis using a PAM-modified Rink amide resin that allows the formation of a peptide ester suitable for subtilisin ligation. The 12-residue acyl donor peptide ester is then ligated to a 3-residue acyl acceptor glycopeptide amide using subtilisin (EC 3.4.21.62) in a buffered mixture of water and DMF (1:9).
Methods Mol Biol 2004
PMID:Subtilisin-catalyzed glycopeptide condensation. 1519 18

Many phylogenetic inference methods are based on Markov models of sequence evolution. These are usually expressed in terms of a matrix (Q) of instantaneous rates of change but some models of amino acid replacement, most notably the PAM model of Dayhoff and colleagues, were originally published only in terms of time-dependent probability matrices (P(t)). Previously published methods for deriving Q have used eigen-decomposition of an approximation to P(t). We show that the commonly used value of t is too large to ensure convergence of the estimates of elements of Q. We describe two simpler alternative methods for deriving Q from information such as that published by Dayhoff and colleagues. Neither of these methods requires approximation or eigen-decomposition. We identify the methods used to derive various different versions of the Dayhoff model in current software, perform a comparison of existing and new implementations, and, to facilitate agreement among scientists using supposedly identical models, recommend that one of the new methods be used as a standard.
Mol Biol Evol 2005 Feb
PMID:Different versions of the Dayhoff rate matrix. 1548 31

Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the COOH-terminal alpha-amidation of peptidylglycine substrates, yielding amidated products. We have previously reported a putative regulatory RNA binding protein (PAM mRNA-BP) that binds specifically to the 3' untranslated region (UTR) of PAM-mRNA. Here, the PAM mRNA-BP was isolated and revealed to be La protein using affinity purification onto a 3' UTR PAM RNA, followed by tandem mass spectrometry identification. We determined that the core binding sequence is approximately 15-nucleotides (nt) long and is located 471 nt downstream of the stop codon. Moreover, we identified the La autoantigen as a protein that specifically binds the 3' UTR of PAM mRNA in vivo and in vitro. Furthermore, La protein overexpression caused a nuclear retention of PAM mRNAs and resulted in the down-regulation of endogenous PAM activity. Most interestingly, the nuclear retention of PAM mRNA is lost upon expressing the La proteins that lack a conserved nuclear retention element, suggesting a direct association between PAM mRNA and La protein in vivo. Reporter assays using a chimeric mRNA that combined luciferase and the 3' UTR of PAM mRNA demonstrated a decrease of the reporter activity due to an increase in the nuclear localization of reporter mRNAs, while the deletion of the 15-nt La binding site led to their clear-cut cytoplasmic relocalization. The results suggest an important role for the La protein in the modulation of PAM expression, possibly by mechanisms that involve a nuclear retention and perhaps a processing of pre-PAM mRNA molecules.
Mol Cell Biol 2005 Sep
PMID:Mammalian peptidylglycine alpha-amidating monooxygenase mRNA expression can be modulated by the La autoantigen. 1610 99

We employed chlorophyll a fluorometry in order to measure the evolution of turgor threshold (intracellular osmolality) during the adaptation of two genetic transformants of the freshwater cyanobacterium Synechococcus sp. PCC7942 to unfavorable external salinity: PAMCOD cells which oxidize imported choline and accumulate approx. 0.06-0.08 M glycine betaine; and PAM cells which do not oxidize choline [Deshnium et al. (1995a) Plant Mol Biol 29: 897-909]. Turgor thresholds increased linearly (a) with the NaCl concentration in the culture, and (b) with the molar sucrose/chlorophyll a ratio in the cell. PAMCOD cells could proliferate in culture medium containing 0.4 M NaCl (external osmolality, 0.815 Osm kg(-1)), after a lag period, during which intracellular sucrose rose to 10 mol (mol Chl a)(-1), or more, and turgor threshold (cytoplasmic osmolality) exceeded 1 Osm kg(-1). At comparative conditions, PAM cells accumulated approx. half as much sucrose, and attained approx. half as high turgor thresholds as the PAMCOD cells, but they did not proliferate. These results indicate that glycine betaine improved the salinity tolerance of the PAMCOD cells synergistically, by means of two effects that implicate sucrose, the main organic osmolyte of Synechocccus: enhancement of sucrose biosynthesis, and/or alleviation of sucrose toxicity.
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PMID:Cell turgor: A critical factor for the proliferation of cyanobacteria at unfavorable salinity. 1622 82

A novel core/shell organic nanoparticles, anthracene/poly-acrylamide (AN/PAM), has been prepared successfully. Based on the fluorescence quenching of AN/PAM nanoparticles by Cr(VI), a method for the selective determination of Cr(VI), without separation of Cr(VI) in water, was developed. Furthermore, the reaction mechanism between nano-AN/PAM and Cr(VI) was also discussed. The synthesis and reaction conditions were investigated in detail. The assay is characterized by short reaction time, very few interference stable fluorescence signals, simple instruments and sensitivity. Under optical experimental conditions, a limit of detection of 0.02 microg/ml was achieved. The calibration curve was linear over the concentration range 0.04-2.00 microg/ml with a correlation coefficient of 0.9924. The proposed method has been applied to the selective quantification of Cr(VI) in synthetic samples and waste-water samples with the satisfactory results.
Spectrochim Acta A Mol Biomol Spectrosc 2005 Nov
PMID:Preparation and application of a novel core/shell organic nanoparticle as a fluorescence probe in the selective determination of Cr(VI). 1625 60

In an attempt to identify a sensitive and improved marker of mammalian copper status during neonatal development experiments compared two plasma cuproenzymes, peptidylglycine alpha-amidating monooxygenase (PAM ), an enzyme involved in peptide posttranslational activation, to ceruloplasmin (Cp), a ferroxidase involved in iron mobilization. Dietary Cu deficiency (Cu-) was studied in dams and offspring at postnatal age 3 (P3), P12, and P28. Rodent Cp activity rose during lactation whereas PAM activity fell. Reduction in Cp activity was more severe than reduction in PAM activity in Cu- offspring and dams. Cp activity was greater in rats than mice whereas PAM activity was similar in adults but greater in mouse than rat pups. Both cuproenzymes changed during neonatal development and when dietary copper was limiting. With proper controls, each enzyme can be used to assess copper status.
Comp Biochem Physiol B Biochem Mol Biol 2006 Mar
PMID:Plasma peptidylglycine alpha-amidating monooxygenase (PAM) and ceruloplasmin are affected by age and copper status in rats and mice. 1644 35

The American Women's Health Initiative study published in July 2002 caused considerable concern among hormone replacement therapy (HRT) users and prescribers in many countries. This study is an exploratory research comparing the genome-wide expression profile in whole-blood samples according to HRT use. Within the Norwegian Women and Cancer study, 100 postmenopausal women (50 HRT users and 50 non-HRT users) born between 1943 and 1949 with normal to high body mass index and no other medication use were selected. After total RNA extraction, amplification, and labeling, the samples were hybridized together with a common reference (Universal human reference RNA, Stratagen) to Agilent Human 1A oligoarrays (G4110b, Agilent Technologies) containing 20,173 unique genes. Differentially expressed genes were used to build a classifier using the nearest shrunken centroid method (PAM). Then, we tested the significant changes in single genes by different methods like t test, Significance Analysis of Microarrays, and Bayesian ANOVA analysis. Results did not reveal any distinct gene list which predicted accurately HRT exposure (error rate, 0.40). Classifier performance slightly improved (error rate, 0.26) including only women who were using continuous combined HRT treatment. According to the small amplitude of expression alterations observed in whole blood, more quantitative technique and larger sample sizes will be needed to be able to investigate whether significant single genes are differentially expressed in HRT versus non-HRT users. Taken cautiously, significant enrichments in biological process of genes with small changes after HRT use were observed (e.g., receptor and transporter activities, immune response, frizzled signaling pathway, actin filament organization, and glycogen metabolism).
Mol Cancer Ther 2006 Apr
PMID:Gene expression profiling of whole-blood samples from women exposed to hormone replacement therapy. 1664 56


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