Disease relevance of Npepps

• Here we show that puromycin-sensitive aminopeptidase (Psa)-deficient mice display female infertility that results from impaired formation of CLP [1].
• A mouse mutation, termed goku, was generated by a gene-trap strategy. goku homozygous mice showed dwarfism, a marked increase in anxiety, and an analgesic effect [2].
• A genomic screen for modifiers of tauopathy identifies puromycin-sensitive aminopeptidase as an inhibitor of tau-induced neurodegeneration [3].
• We showed that a Zn chelator, N,N,N,N-tetrakis (2-pyridylmethyl) ethylenediamine, inhibited in vivo allergic reactions such as PCA and PSA [4].
• Decreased cytotoxic T cell activity generated by co-administration of PSA vaccine and CpG ODN is associated with increased tumor protection in a mouse model of prostate cancer [5].

High impact information on Npepps

• We used a cross species functional genomic approach to analyze gene expression in multiple brain regions in mouse, in parallel with validation in Drosophila, to identify tau modifiers, including the highly conserved protein puromycin-sensitive aminopeptidase (PSA/Npepps) [3].
• We also confirmed the importance of the Psa permease in systemic virulence and resistance to superoxide and hydrogen peroxide, as well as demonstrating a role in nasopharyngeal colonization for the first time [6].
• In the present study we show that puromycin-sensitive aminopeptidase (Psa)-deficient mice are infertile, lack copulatory behavior, and have impaired spermatogenesis [7].
• Considering the strong expression of the Psa gene in the brain and Sertoli cells and the degenerative morphology of Sertoli cells in Psa-deficient mice, Psa may participate in testosterone-mediated reproductive signal pathways in the brain and testis [7].
• In the present study, we investigated the effect on spatial memory consolidation of a PSA gain of function by injecting a PSA mimetic peptide (termed pr2) into the dorsal hippocampus [8].

Biological context of Npepps

• Puromycin-sensitive aminopeptidase gene (Psa) maps to mouse chromosome 11 [9].
• RESULTS: Expression of an adenovirally-delivered luciferase reporter gene in prostate tumor cells in bigenic mice (PSA/hCAR + TRAMP) was enhanced compared to the level in tumor cells lacking the PSA/hCAR transgene [10].
• Polysialylated neural cell adhesion molecule (PSA-NCAM) is predominantly expressed during development where it regulates biological functions including axon targeting and neuronal precursor cell migration [11].
• No close relationship was found between the fluxes of piroxicam or PX-EA salts from saturated solutions and from PSA matrices containing the same enhancer [12].
• The effects of salt formation on the percutaneous absorption of piroxicam through hairless mouse skin from a pressure sensitive adhesive (PSA) matrix were investigated [12].

Anatomical context of Npepps

• Together with the finding that the Psa gene is strongly expressed in the brain, especially in the striatum and hippocampus, these results suggest that the Psa gene is required for normal growth and the behavior associated with anxiety and pain [2].
• Here, we report the pattern of expression of NCAM and PSA-NCAM in the anterior lobe (AL) of the pituitary gland of the adult mouse [13].
• PSA NCAM and MyoD1 had gradually disappeared from the muscle fibers by the seventh day, by which time, the expression of the other developmentally regulated proteins had also decreased [14].
• The results show that NCAM, PSA NCAM and desmin were already present on the first day after injury in the presumptive myoblasts [14].
• Some of the lectins tested in this study (SBA, succ-WGA, and PSA) labeled the sensory cells of the cochlea around birth [15].

Associations of Npepps with chemical compounds

• The NCAM, encoded by a single gene, is represented by several isoforms that differ with regard to their content of alpha-2,8-linked sialic acid residues (PSA) on their extracellular domain [8].
• (4) Gradual PSA-NCAM expression was observed in the lateral portion of Kölliker's organ, and the intense PSA-NCAM expression was seen surrounding the IHCs [16].
• Analysis of bromodeoxyuridine (BrdU) incorporation shows that the presence of PSA-NCAM on corticotropes is not related to proliferation but most likely to their functional properties [13].
• Maximum piroxicam flux was obtained when PX-MEA/PX-TEA (4:6, v/v) was incorporated into a PSA matrix containing Crovol PK40 [12].
• The order of the permeation rates of piroxicam and PX-EA salts from the PSA matrix was piroxicam-monoethanolamine salt (PX-MEA)>piroxicam-diethanolamine salt (PX-DEA)>piroxicam>piroxicam-triethanolamine salt (PX-TEA) [12].

Analytical, diagnostic and therapeutic context of Npepps

• Athymic mice bearing s.c. androgen receptor-negative and PSA-negative PC-3 xenografts responded to a single intratumoral administration of 2 x 10(9) plaque-forming unit(s) of Ad-OC-E1a [17].

References