Five novel peptides were identified in the brains of mice lacking active carboxypeptidase E, a neuropeptide-processing enzyme. These are produced from single precursor, termed proSAAS, which is present human, mouse, and rat. ProSAAS mRNA expressed primarily brain other neuroendocrine tissues (pituitary, adrenal, pancreas); within brain, broadly distributed among neurons. When AtT-20 cells, proSAAS secreted via regulated pathway also processed at paired-basic cleavage sites into smaller...

Plasma HDL levels are inversely related to the incidence of atherosclerotic disease. Some atheroprotective effects likely mediated via preservation EC function. Whether beneficial on ECs depend its involvement in cholesterol efflux ATP-binding cassette transporters ABCA1 and ABCG1, which promote oxysterols from macrophages, has not been investigated. To address this, we assessed endothelial function Abca1–/–, Abcg1–/–, Abca1–/–Abcg1–/– mice fed either a high-cholesterol diet (HCD) or Western...

Studies of diabetic vascular disease have traditionally used murine models type 1 diabetes and genetic 2 diabetes. Because the majority patients with diet induced obesity, we sought to study effect on arterial in a mouse model obesity/diabetes. C57Bl/6 mice fed high-fat for 9 weeks developed characterized by elevated body weight, hyperglycemia, hyperinsulinemia. Arteries from exhibited marked decrease endothelium-dependent vasodilation, modest endothelium independent an increase sensitivity...

Cpe fat /Cpe mice have a naturally occurring point mutation within the carboxypeptidase E gene that inactivates this enzyme, leading to an accumulation of many neuroendocrine peptides containing C-terminal basic residues. These processing intermediates can be readily purified on anhydrotrypsin affinity resin. Using MS obtain molecular mass and partial sequence information, more than 100 been identified. represent fragments 16 known secretory pathway proteins, including proenkephalin,...

Phage therapeutics offer a potentially powerful approach for combating multidrug-resistant bacterial infections. However, to be effective, phage therapy must overcome existing and developing resistance. While cocktails can reduce this risk by targeting multiple receptors in single therapeutic, bacteria have mechanisms of resistance beyond receptor modification. A rapidly growing body knowledge describes broad varied arsenal antiphage systems encoded counter infection. We sought understand...

ABSTRACT We describe the genomes of three lytic Pseudomonas aeruginosa phages genus Phikmvvirus . The vB_Pae4841-AFR43, vB_Pae10145-KEN1, and vB_Pae9718-KEN10 consist 43,426, 43,406, 43,118 bp, with 62.4%, 62.3%, 62.2% GC content, contain 63, 66, 64 coding sequences, respectively, no tRNA genes.

ProSAAS is a recently discovered 26-kDa neuroendocrine protein that was previously found to inhibit prohormone convertase (PC) 1 and not PC2. In the present study, specificity of proSAAS toward other members family determined. Two microm selectively inhibits PC1 but furin, PACE4, PC5A, or PC7. The inhibitory region mapped an 8-12-residue near C terminus includes critical Lys-Arg sequence. Synthetic peptides corresponding this are competitive inhibitors with apparent K(i) values 14-40 nm....

Abstract: Prodynorphin, a multifunctional precursor of several important opioid peptides, is expressed widely in the CNS. It processed at specific single and paired basic sites to generate various biologically active products. Among prohormone convertases (PCs), PC1 PC2 are neuroendocrine tissues have been proposed be major involved biosynthesis hormonal neural peptides. In this study we examined physiological involvement generation dynorphin (Dyn) peptides mice lacking as result gene...

J. Neurochem. (2010) 113 , 1275–1284. Abstract Mice with a targeted mutation in proSAAS have been generated to investigate whether peptides derived from this precursor could function as an inhibitor of prohormone convertase 1/3 (PC1/3) vivo well determine any alternate roles for nervous and endocrine tissues. Fetal mice lacking exhibit complete, adult‐like processing prodynorphin the prenatal brain instead incomplete seen brains wild‐type fetal where inhibitory intermediates are transiently...

ProSAAS is a neuroendocrine peptide precursor that potently inhibits prohormone convertase 1 in vitro. To explore the function of proSAAS and its derived peptides, transgenic mice were created which express using beta-actin promoter. The body weight was normal until approximately 10-12 weeks, then increased 30-50% over wild-type littermates. Adult had fat mass twice mice, fasting blood glucose levels slightly elevated. In pituitary, several fully processed peptides not reduced compared with...

ABSTRACT We describe the genome of a lytic phage EKq1 isolated on Klebsiella quasipneumoniae , with activity against pneumoniae . is an unclassified representative class Caudoviricetes, similar to phages VLCpiS8c, phiKp_7-2, and vB_KleS-HSE3. The 48,244-bp has GC content 56.43% 63 predicted protein-coding genes.

A spontaneous point mutation in the coding region of carboxypeptidase E (CPE) gene results a loss CPE activity that correlates with development late onset obesity (Nagert, J. K., Fricker, L. D., Varlamov, O., Nishina, P. M., Rouille, Y., Steiner, D. F., Carroll, R. J., Paigen, B. and Leiter, E. H. (1995) Nat. Genet. 10, 135–142). Examination level neuropeptides these mice showed decrease mature bioactive peptides as result both prohormone convertase activities. defect is not expected to...

Identification of arterial genes and pathways altered in obesity diabetes.Aortic gene expression profiles obese diabetic db/db, high-fat diet-fed C57BL/6J, control mice were obtained using mouse Affymetrix arrays. Neuronatin (Nnat) was selected for further analysis. To determine the function Nnat, a recombinant adenovirus (Ad-Nnat) used to overexpress Nnat primary endothelial cells aorta vivo.Nnat, unknown vascular function, upregulated aortas db/db mice. increased cells. protein localized...

ProSAAS is a newly discovered protein with neuroendocrine distribution generally similar to that of prohormone convertase 1 (PC1), peptide-processing endopeptidase. Several proSAAS-derived peptides were previously identified in the brain and pituitary Cpe(fat)/Cpe(fat) mouse based on accumulation C-terminally extended due absence enzymatically active carboxypeptidase E, exopeptidase. In present study, antisera against different regions proSAAS used develop radioimmunoassays examine...

Most neuroendocrine peptides are generated by proteolysis of the precursors at basic residue cleavage sites. Prohormone convertases belonging to subtilisin family serine proteases primarily responsible for processing these "classical sites." In addition classical cleavages, a subset bioactive is "nonclassical" The cleavages have not been well explored. Members several metalloprotease families proposed be involved in nonclassical processing. Among them, endothelin-converting enzyme-2 (ECE-2)...

A novel cDNA, designated human metalloendoprotease 1 (hMP1), was identified on the basis of homology to known metalloendoproteases pitrilysin family. The full-length MP1 codes for a protein with an open reading frame 1038 amino acids. N-terminal region contains HXXEH(X)76E catalytic domain that is conserved in members family, namely insulin-degrading enzyme and NRD convertase. hMP1 mRNA expressed number cell lines tissues as single species about 3.4 kb. expression higher muscle heart than...

ProSAAS, a recently discovered granin-like protein, potently inhibits prohormone convertase (PC)1, and might also perform additional functions. In the present study, processing of proSAAS was compared in two neuroendocrine cell lines overexpressing this protein: AtT-20 mouse pituitary corticotrophic line PC12 rat adrenal phaeochromocytoma line. The examined by pulse–chase analysis using [3H]leucine, MS, chromatography radioimmunoassay. Various smaller forms were detected, including peptides...

ProSAAS, a recently discovered granin-like protein, potently inhibits prohormone convertase (PC)1, and might also perform additional functions. In the present study, processing of proSAAS was compared in two neuroendocrine cell lines overexpressing this protein: AtT-20 mouse pituitary corticotrophic line PC12 rat adrenal phaeochromocytoma line. The examined by pulse–chase analysis using [3H]leucine, MS, chromatography radioimmunoassay. Various smaller forms were detected, including peptides...

The N-terminal Zn-finger motif of the beta' subunit RNA polymerase contains two pairs invariant cysteines flanking a moderately well-conserved segment 13 amino acids that is rich in basic residues. Previous work showed replacement certain residues prevented transcription antitermination response to phage HK022 put sites. Nascent binds and modifies transcribing polymerase, so it becomes resistant termination. To characterize Zn finger further, we replaced each with alanine determined effects...

Abstract In vitro assays have demonstrated that peptides derived from the recently–identified proSAAS precursor inhibit prohormone convertase 1 (PC1) suggesting this novel peptide may function as an endogenous inhibitor of PC1. To further understand role in vivo , we investigated expression mRNA and processing during pre‐ early postnatal rodent development. situ hybridization showed that, by embryonic day 12.5 (e12.5) rat, was present essentially all differentiating neurons mantle layer...

We describe the genome of a lytic phage EAb13 isolated from sewage, with broad activity against multidrug-resistant Acinetobacter baumannii. is an unclassified siphovirus. Its consists 82,411 bp, 40.15% GC content, 126 protein-coding sequences, 1 tRNA, and 2,177 bp-long direct terminal repeats.

ABSTRACT The genomes of three Pseudomonas aeruginosa Phikzvirus bacteriophages isolated in Kenya are described. phages vB_PaePAO1-KEN19, vB_Pae3705-KEN49, and vB_Pae10145-KEN51, respectively, had lengths 278,921, 280,231, 280,173 bp, with 36.93%, 36.84%, 36.86% GC content, containing 419, 417, 417 coding sequences (including seven tRNAs each genome).

ABSTRACT We describe the genomes of five lytic Klebsiella pneumoniae myophages, therapeutic candidates, that belong to family Straboviridae and genus Jiaodavirus . The ranged from 165,574 169,768 bp, with ca. 40% GC content, contained 289–300 coding sequences, had 15–16 tRNA genes, no terminal repeats.

Phage therapeutics offer a potentially powerful approach to combat multidrug-resistant bacterial infections. However, be effective, phage therapy must overcome existing and developing resistance. While cocktails can reduce this risk by targeting multiple receptors in single therapeutic, bacteria have mechanisms of resistance beyond receptor modification. A rapidly growing body knowledge describes broad varied arsenal antiphage systems encoded counter infection. We sought understand the types...