Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously showed that bovine apolipoprotein A-II (apoA-II) had antimicrobial activity against Escherichia coli and the yeast Saccharomyces cerevisiae in PBS. We have characterized here the active domain of apoA-II using synthetic peptides. A peptide corresponding to C-terminal residues Leu(49)-Thr(76) exhibited significant antimicrobial activity against E. coli in PBS, but not against S. cerevisiae. Experiments using amino-acid-substituted peptides indicated that the residues Phe(52)-Phe(53)-Lys(54)-Lys(55) are required for the activity. Peptide Leu(49)-Thr(76) induced the release of calcein trapped inside the vesicles whose lipid composition resembles that of E. coli membrane, suggesting that peptide Leu(49)-Thr(76) can destabilize the E. coli membrane. CD measurements showed that the alpha-helicity of peptide Leu(49)-Thr(76) increased from 3.5 to 36% by addition of the vesicles. When E. coli cells were incubated with peptide Leu(49)-Thr(76), some proteins were released to the external medium, probably owing to membrane destabilization caused by the peptide. In electron micrographs of E. coli cells treated with peptide Leu(49)-Thr(76), transparent nucleoids and granulated cytoplasm were observed. Amino acid substitutions, Phe(52)Phe(53)-->AlaAla (Phe(52, 53)-->Ala) in peptide Leu(49)-Thr(76) caused the loss of antimicrobial activity against E. coli, although protein-releasing activity was retained. Electron micrographs of the cells treated with peptide Leu(49)-Thr(76)(Phe(52,53)-->Ala) revealed morphological change only at the nucleoids. Therefore peptide Leu(49)-Thr(76) appears to primarily target the cytoplasm rather than the membrane of E. coli cells.
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PMID:Lipid-binding and antimicrobial properties of synthetic peptides of bovine apolipoprotein A-II. 1043 19

Normothermic ischemia and reperfusion of the liver results in microcirculatory failure followed by necrosis and cell death. Recently, another type of cell death, apoptosis or programmed cell death, was found to be activated during the early phase of reperfusion after liver ischemia. Caspases are cysteine proteinases specifically involved in the initiation and execution phases of apoptosis. The aim of this study was to demonstrate that inhibition of apoptosis by a specific inhibitor of caspases might protect the liver against ischemia/reperfusion injury. Rats were divided into three groups: group 1, control, PBS administration; group 2, Z-Asp-cmk (Z-Asp-2,6-dichlorobenzoyl-oxymethylketone) treatment; group 3, sham-operated control animals. Z-Asp-cmk (0.5 mg Z-Asp-cmk dissolved in 300 microl PBS solution containing 1% DMSO) was injected intravenously, 2 min prior to induction of 120 min ischemia. Survival rates were compared and serum activities of aspartate aminotransferases and alanine aminotransferases were assessed in the blood collected from the suprahepatic vena cava. Histology of the liver was assessed 6 h after the end of ischemia. Apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated dUTP-FITC nick end-labeling method (TUNEL method) and by electrophoresis for analysis of DNA fragmentation. Caspase activity was determined by measuring hydrolysis of the CPP32-like substrate Ac-DEVD-pNA and absorption of paranitroaniline. Z-Asp-cmk treatment significantly increased 7-day survival (95%) compared with that in nontreated rats (30%, P < 0.001). Serum activities of aminotransferases and the extent of liver congestion and necrosis were significantly (P < 0.001) decreased after treatment with Z-Asp-cmk. TUNEL-positive cells were detected 3-6 h after reperfusion in the control group. In Z-Asp-cmk pretreated rats, a dramatic decrease in the number of TUNEL-positive cells was observed. Analysis of DNA fragmentation of freshly isolated hepatocytes confirmed these results. Caspase activity was increased 3-6 h after reperfusion in the control group, but significantly (P < 0.001) decreased after treatment with Z-Asp-cmk. These findings demonstrate that liver injury following ischemia and reperfusion can be prevented by inhibition of caspases. Caspase inhibitors may have important implications for therapy in liver disease and after liver transplantation.
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PMID:Caspase inhibition protects from liver injury following ischemia and reperfusion in rats. 1111 76

Marrow stromal cells (MSCs) transplantation into brain has been employed to treat experimental ischemia. However, MSCs undergo apoptosis and few survive in the ischemic brain. We test the hypotheses that coadministration of bone marrow cells (BMCs) with a cell-permeable inhibitor of caspases, Z-Val-Ala-DL-Asp-fluoromethylketone (Z-VAD), into the ischemic boundary zone (IBZ) of brain promotes BMCs survival and improve outcome. Experimental groups consist of: 24 h after MCAo, either phosphate-buffered saline (PBS, n=4), dead BMC (n=4), fresh BMC (n=10), Z-VAD only (n=4), or BMC with Z-VAD (n=6) were intracerebrally injected. BMCs were harvested from donor adult rats labeled with bromodeoxyuridine (BrdU). Rats were subjected to an adhesive-removal somatosensory and motor-rotarod functional tests before MCAo and at 1 and 7 days after MCAo. Rats treated with a combination of Z-VAD and BMCs exhibited significant improvement in the adhesive-removal test at 7 days compared with the control group (combined MCAo+PBS and MCAo+dead BMC) (p<0.01), and the numbers of BrdU-BMC increased (p<0.05) and apoptotic cells decreased (p<0.05) compared with BMC alone transplantation. Our data suggest that intracerebral coadministration of BMC with Z-VAD enhances the survival of grafted BMC and improves neurological functional recovery after MCAo.
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PMID:Caspase inhibition by Z-VAD increases the survival of grafted bone marrow cells and improves functional outcome after MCAo in rats. 1208 37

We previously showed that bovine apolipoprotein A-II (apoA-II) has antimicrobial activity against Escherichia coli in PBS, and its C-terminal residues 49-76 are responsible for the activity using synthetic peptides. In order to understand the structural requirements of peptide 49-76 for the antimicrobial activity, the N- or C-terminus was truncated and then the charged (Lys or Asp) or Ser residues were replaced by Ala. Deletion of the first or last three amino acids and replacement of Lys-54/55 or 71/72 by Ala caused a substantial decreases in alpha-helical content in 50% TFE, showing the possible presence of helices in N- and C-terminal regions, respectively. The anti-Escherichia coli activity of the peptide correlated with its liposome-binding activity. Replacement of Lys-54/55 or 71/72 by Ala resulted in an almost complete loss of anti-E. coli activity with a substantial decrease in liposome-binding activity. Moreover, deletion of the last three amino acids caused a reduction to 1/17 of the original anti-E. coli activity with a moderate decrease in liposome-binding activity. In contrast, replacement of Ser-65/66, Asp-59, or Asp-69 by Ala hardly affected the anti-E. coli activity. These findings suggest that Lys-54/55 and Lys-71/72 on the putative helices are critical for antimicrobial activity, and the C-terminal 3 amino acids are important for the structural integrity of the C-terminal region for effective antimicrobial activity.
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PMID:Structure-activity analysis of an antimicrobial peptide derived from bovine apolipoprotein A-II. 1209 67

Soluble antigens exist in the bile of rabbits infected with Eimeria stiedai (E. stiedai) in the acute phase, and rabbits immunized with the antigens show resistance against the infection. In this study, the liver function of rabbits immunized either with the soluble antigens or PBS were examined following the parasite challenge. Rabbits immunized with PBS shed a number of oocysts and showed an increase in r-glutamyltransferase (GGT) activity and a decrease in blood Indocyanine green (ICG) clearance. However, rabbits immunized with the soluble antigens shed a lower number of oocysts and showed a transient increase of alanine-aminotransferase (ALT) activity on Day 8 post-challenge (p.c.). The blood Indocyanine green clearance of the rabbits showed no change throughout the experiment. By histopathological observation of the liver, a number of merozoites were found in the biliary ducts on Day 8 post-challenge in the non-immunized rabbits. In contrast, a number of lymphocytes and neutrophilic leukocytes assembled around the biliary ducts of the immunized rabbits, but few parasites were found there on Day 8 post-challenge. These results suggest that the soluble antigens stimulate local immune reactions, for example around the biliary ducts, resulting in elimination of the parasite's development.
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PMID:Relationship between liver disorders and protection against Eimeria stiedai infection in rabbits immunized with soluble antigens from the bile of infected rabbits. 1253

Goblet cell hyperplasia in the superficial airway epithelia is a signature pathological feature of chronic bronchitis and cystic fibrosis. In these chronic inflammatory airway diseases, neutrophil elastase (NE) is found in high concentrations in the epithelial lining fluid. NE has been reported to trigger mucin secretion and increase mucin gene expression in vitro. We hypothesized that chronic NE exposure to murine airways in vivo would induce goblet cell metaplasia. Human NE (50 microg) or PBS saline was aspirated intratracheally by male Balb/c (6 wk of age) mice on days 1, 4, and 7. On days 8, 11, and 14, lung tissues for histology and bronchoalveolar lavage (BAL) samples for cell counts and cytokine levels were obtained. NE induced Muc5ac mRNA and protein expression and goblet cell metaplasia on days 8, 11, and 14. These cellular changes were the result of proteolytic activity, since the addition of an elastase inhibitor, methoxysuccinyl Ala-Ala-Pro-Val chloromethylketone (AAPV-CMK), blocked NE-induced Muc5ac expression and goblet cell metaplasia. NE significantly increased keratinocyte-derived chemokine and IL-5 in BAL and increased lung tissue inflammation and BAL leukocyte counts. The addition of AAPV-CMK reduced these measures of inflammation to control levels. These experiments suggest that NE proteolytic activity initiates an inflammatory process leading to goblet cell metaplasia.
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PMID:Neutrophil elastase induces mucus cell metaplasia in mouse lung. 1527 79

PEGylated polyamidoamine (PAMAM) dendrimers as drug carriers have been a topic of interest because of their biomedically favorable features, including minimal toxicity, reduced immunogenicity, and excellent solubility in aqueous and most organic solutions. A PEG shell on dendrimer surface may provide steric hindrance, known as stealth properties of PEG, to stabilize drug molecules to be delivered. In this article, the effects of PEG and coupling sequence of drug, PEG, and dendrimer in modulating the stability of delivered drug molecules were evaluated. N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide was chosen as a model peptide. Dendritic peptides, that is, peptide-dendrimer, peptide-PAMAM-PEG, and peptide-PEG-dendrimer, were constructed based on Starbursttrade mark G3.0 PAMAM dendrimer and characterized by (1)H-NMR spectroscopy. Hydrolysis of dendritic peptides was catalyzed by alpha-chymotrypsin in pH 7.4 PBS buffer containing 5% DMF (v/v) at room temperature. The enzymatic stability of dendritic peptides was peptide-PAMAM-PEG > peptide-PAMAM > free peptide > peptide-PEG-PAMAM. The ratio of PEG/peptide could be reduced for increasing peptide loading while maintaining the delivered peptides' relatively high enzymatic stability. The quantitative analysis of dendritic peptide/enzyme interactions provided the understandings of the molecular structure/stability relationships of dendrimer/drug for the design of an optimal PEGylated dendrimer-based drug-delivery system.
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PMID:In vitro enzymatic stability of dendritic peptides. 1627 Mar 46

Poly(L-valine-L-proline-L-alanine-L-valine-L-glycine) (VPAVG) is a new kind of proteinaceous polymer belonging to the Elastin-like family. These polymers are based on the recurrence of certain short peptide monomers that are considered as "building blocks" in the natural elastin. This smart thermoresponsive polymer has the ability to self-associate at physiological temperature to form aggregates with about 60% in water. This ability can be harnessed to prepare microparticles loaded with an active substance. The aim of this report is to evaluate, from the results of the experiment conducted, the biocompatibility of microparticles prepared from poly(VPAVG). We have studied the cytotoxic effects of microparticles, edema formation after subcutaneous injection (1 and 2.5 mg) in rats (n = 6), and also intraocular tolerance after the intravitreal injection of 2.5 mg of poly(VPAVG) microparticles into pigmented rabbits (n = 12). The polymer did not induce any cytotoxicity or nonspecific depression of cellular respiration on macrophages under the range of polymer concentrations investigated in this study (20, 30, 40, and 60 mg/mL). We observed no inflammatory response to microparticles after subcutaneous injection in the hind-paw of rats, with no significant differences between the control group (PBS) and experimental groups. Anterior and posterior segment signs were evaluated after intraocular injection of poly(VPAVG) microparticles. Only a few eyes (2/11) of the experimental group presented inflammation signs at day 28 postinjection. Nevertheless, 45% (5/11) of the eyes receiving microparticles showed tractional retinal detachment. The results observed in this work suggested certain fibroblastic activity induced by poly(VPAVG) microparticles after their intraocular injection.
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PMID:Biocompatibility of elastin-like polymer poly(VPAVG) microparticles: in vitro and in vivo studies. 1664 66

An intelligent biosynthetic nanobiomaterial (IBN) platform was explored for drug delivery applications for hyperthermic combination chemotherapy and thermal drug targeting. Geldanamycin (GA), a heat shock protein 90 inhibitor, was conjugated to novel thermosensitive poly(K)(8)-poly(VPGXG)(60) block copolymers [K(8)-ELP(1-60)] with guest residues as valine, alanine and glycine in a 5:2:3 ratio at the 'X' position. The conjugates were completely soluble in PBS and showed a characteristic thermosensitive inverse phase transition. [K(8)-ELP(1-60)]-GA conjugate nanoparticles showed a size ranging from 50 to 200 nm depending upon temperature. Relevant to systemic drug delivery in vivo, these IBNs stably disperse in aqueous solution. Cytotoxicity assays have shown that the IBN from [K(8)-ELP(1-60)]-GA conjugates exhibits effective hyperthermic combination chemotherapy with facile heat modulation.
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PMID:Intelligent biosynthetic nanobiomaterials for hyperthermic combination chemotherapy and thermal drug targeting of HSP90 inhibitor geldanamycin. 1765 57

Kallikrein is a multitalented enzyme in hemostasis and inflammation. Normally, kallikrein is formed in intrinsic hemostasis and activates factor XII. A total of 10 microL of 0 to 100 microg/mL human plasma kallikrein in 6% human albumin-PBS were incubated with 90 microL 111.1 microg/mL prothrombin in 6% human albumin in absence and presence of 23 mM Ca(++). After 0 to 64 minutes (37 degrees C), 100 microL of 2.5 M arginine, pH 9, were added. Fifty microliters of 0.72 mM HD-CHG-Ala-Arg-pNA in 1.36 M arginine were added and increase in absorbance at 405 nm was determined. Within 8 minutes (37 degrees C), 1 microg/mL kallikrein, ie, 2.5% of the normal plasmatic prekallikrein concentration, generates approximately 3 mIU/mL thrombin in absence and 27 mIU/mL thrombin in presence of Ca(++). Kallikrein can directly activate prothrombin; there is a shortcut in the intrinsic hemostasis system that generates catalytic amounts of thrombin without following the known intrinsic clotting pathway.
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PMID:Kallikrein activates prothrombin. 1816 May 76


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