BACKGROUND: According to the notion of the immunoregulatory functions of moxifloxacin (MFX), the effect of MFX on the neutrophilic respiratory burst in conjunction with the expression of cytosolic phospholipase A2 (cPLA2) was investigated. METHODS: The effects and possible mechanisms of MFX on neutrophilic respiratory burst in oleic acid (OA)-induced acutely injured rats lung and OA-stimulated, isolated murine neutrophils were probed, associated with the expression of cytosolic phospholipase A2 in vivo and in vitro. RESULTS: In the OA-induced acutely-injured lungs, neutrophils were accumulated, which was attenuated by MFX. The parameters denoting a neutrophilic respiratory burst, such as nitro blue tetrazolium reaction, cytochrome-c reduction, neutrophil aggregation, H2O2 production in neutrophils revealed increased neutrophilic respiratory burst by OA, and MFX decreased all of these parameters. In addition, the enhanced expression of cPLA2 in the lung and isolated murine neutrophils by OA were decreased by MFX. CONCLUSION: MFX suppresses the OA-induced neutrophilic respiratory burst by the suppression of cPLA2 in neutrophils.
Animals ; Aza Compounds ; Cytosol ; Lung ; Neutrophils ; Oleic Acid ; Phospholipases ; Phospholipases A2 ; Phospholipases A2, Cytosolic ; Quinolines ; Rats ; Respiratory Burst

Secretin, a gastrointestinal peptide, has been found to be expressed in mouse endometrial stromal cells (mESCs) during early pregnancy. In order to further investigate the function of secretin during embryo implantation, the expression levels of secretin, secretin receptor, cytosolic phospholipase A(cPLA) and membrane prostaglandin E synthase 1 (mPGEs-1) were detected in the mice uterus from day 4 to 8 of pregnancy by real-time PCR, ELISA and in situ hybridization. mESCs isolated and cultured from day 4 of pregnancy were transfected with secretin expression vectors or treated with H89, a PKA inhibitor. Then the expression levels of cPLA, mPGEs-1 and cAMP responsive element-binding protein (CREB) were detected by real-time PCR and Western blot. The concentration of prostaglandin E2 (PGE) in the supernatant was determined by ELISA. The result showed that secretin, cPLAand mPGEs-1 mRNA expression increased gradually in implantation sites from day 5 to day 7 of pregnancy with the same tendency. The secretin levels in serum were significantly higher on days 6, 7 and 8 of pregnancy than that on day 5 of pregnancy. The concentration of secretin was significantly higher in implantation sites on days 6, 7 than that in non-implantation site on day 5. Transfection of secretin expression vector promoted cPLA, p-cPLAand mPGEs-1 expressions in mESCs, but not PGElevel in the supernatant. H89 could effectively inhibit the expression of CREB, p-CREB, p-cPLAand cPLAinduced by secretin. The results showed that the increased secretin expression in mESCs during embryo implantation may promote p-cPLA, cPLAand mPGEs-1 expression, and the promotion may be through PKA signaling pathway.
Animals ; Blotting, Western ; Cyclic AMP Response Element-Binding Protein ; Dinoprostone ; Female ; Mice ; Phospholipases A2, Cytosolic ; Pregnancy ; Prostaglandin-E Synthases ; Real-Time Polymerase Chain Reaction ; Secretin ; Stromal Cells ; Uterus

OBJECTIVETo investigate the genetic association between the polymorphism of cytosolic phospholipase A2 (cPLA2) family genes and schizophrenia in the North Han Chinese.

METHODSMethod of polymerase chain reaction-based ligase detection reaction (PCR-LDR) was applied to genotype 10 single nucleotide polymorphisms (SNPs) of cPLA2 family genes among 201 pedigrees consisting of fathers, mothers and affected offsprings with schizophrenia. Haplotype relative risk (HRR) test, transmission disequilibrium test (TDT), haplotype transmission analysis and multiple locus analysis were conducted to analyze the genotyping data.

RESULTSThe genotypic frequency of cPLA2 gene did not deviate from Hardy-Weinberg equilibrium in both case and control groups. HRR and TDT showed that the 10 SNPs were not associated with schizophrenia (P > 0.05). Analysis for haplotype transmission showed that no haplotype systems was associated with schizophrenia (P > 0.05). Results from COA and COG tests showed a disease association for the rs2162886-rs1668589, rs891014-rs1668589 and rs2307279-rs7542180 combinations (chi2 = 6.913, P = 0.032; chi2 = 8.393, P = 0.015; chi2 = 8.447, P = 0.038).

CONCLUSIONMany loci in the cPLA2 family genes were associated with schizophrenic.

Adolescent ; Adult ; Asian Continental Ancestry Group ; genetics ; China ; epidemiology ; Female ; Gene Frequency ; genetics ; Genetic Predisposition to Disease ; genetics ; Genotype ; Haplotypes ; genetics ; Humans ; Male ; Phospholipases A2, Cytosolic ; genetics ; Polymorphism, Single Nucleotide ; genetics ; Schizophrenia ; epidemiology ; genetics ; Young Adult

Gene Expression ; Humans ; Neoplasms ; Peroxiredoxin VI

OBJECTIVE: To study the expression of Peroxiredoxin-6 (Prdx6) gene in elderly patients with acute myeloid leukemia (AML) and its clinical significance. METHODS: The expression level of Prdx6 in bone marrow cells of 33 cases of AML, 8 cases of CML and 11 cases of other blood diseases was detected by PCR. The correlation of the abnormal expression of Prdx6 with patient age and blood routine parameters was further analyzed. RESULTS: the expression level of Prdx6 in elderly patients with AML (≥60 years) was significantly lower than that in younger patients (＜60 years) (P＜0.05); the expression level of Prdx6 in low WBC (≤1×10/L) group was lower than that in medium WBC (1-10×10/L) group or high WBC (＞10×10/L) group (P＜0.05); the proportion of WBC count (≤1×10/L) in elderly patients with AML reached 38.5%, which was significantly higher than that in younger patients (5%) (P＜0.05); the overall survival (OS) rate of elderly patients was lower than that of younger patients (P＜0.05). CONCLUSION The expression of Prdx6 in elderly patients with AML is low, moreover, it relates with low value of WBC in peripheral blood, suggesting that it may be one of poor prognostic factors for the elderly patients with AML.
Aged ; Bone Marrow Cells ; Humans ; Leukemia, Myeloid, Acute ; Leukocyte Count ; Peroxiredoxin VI ; genetics ; metabolism ; Prognosis

Animals ; Cardiovascular System ; chemistry ; Female ; Group II Phospholipases A2 ; blood ; Group IV Phospholipases A2 ; blood ; Group V Phospholipases A2 ; blood ; Group X Phospholipases A2 ; blood ; Male ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar

PURPOSE: The purpose of this study was to identify Radiosensitivity of proteins in tissues with different radiosensitivity. MATERIALS AND METHODS: C3H/HeJ mice were exposed to 10 Gy. The mice were sacrifiud 8 hrs after radiation. Their spleen and liver tissues were collected and analyzed histologicaly for apoptosis. The expressions of radiosusceptibility protein were analyzed by 2-dimensional electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. RESULTS: The peak of apoptosis levels were 35.3+/-1.7% in spleen and 0.6+/-0.2% in liver at 8 hrs after radiation. Liver, radioresistant tissues, showed that the levels of ROS metabolism related to proteins such as cytochromm c, glutathione S transferase, NADH dehydrogenase, riken cDNA and peroxiredoxin VI increased after radiation. The expression of cytochrome c increased significantly in spleen and liver tissues after radiation. In spleen, radiosensitivity tissue, the identified proteins showed a significantly quantitative alteration following radiation. It was categorized as signal transduction, apoptosis, cytokine, Ca signal related protein, stress-related protein, cytoskeletal regulation, ROS metabolism, and others. CONCLUSION: Differences of radiation-induced apoptosis by tissues specifted were coupled with the induction of related radiosensitivity and radioresistant proteins. The result suggests that apoptosis relate protein and redox proteins play important roles in this radiosusceptibility.
Animals ; Apoptosis ; Cytochromes c ; DNA, Complementary ; Electrophoresis ; Glutathione Transferase ; Liver ; Mass Spectrometry ; Metabolism ; Mice ; NADH Dehydrogenase ; Oxidation-Reduction ; Peroxiredoxin VI ; Proteomics* ; Radiation Tolerance* ; Signal Transduction ; Spleen

OBJECTIVETo confirm the antioxidant protective effect of peroxiredoxin 6 (Prdx6) in acute lung injury in mice.

METHODSLung injury or lung alveolar type II epithelial cell (AEC II) injury models were induced in mice by 100% O2 exposure or H2O2 treatments. Mice and AEC II cell survival rate or BALF analysis were applied for evaluating the degree of acute lung injury. Western Blot assay was used to determine Prdx6 or Gpx1 protein expression in lung. Annexin V staining method was applied to detect cell apoptosis on cultured AEC II cell, and thiobarbituric acid reactive substance (TBARS) measurement and diphenyl-1-pyrenyl phospholine (DPPP) assays were separately used to measure the level of lipid peroxidation in mice lung and AEC II cell membrane.

RESULTSUnder 100% O2 exposure, Prdx6-/- mice presented 24 h shorter survival time compared to wild type (WT) mice, on the contrary, Prdx6 gene over-expressed (Tg Prdx6) mice showed enhanced mice survival; meanwhile, the degree of AEC II cell injury had H2O2-dose dependent pattern with interactive relationship of Prdx6 protection. Under 100% O2 exposure for 72 h, it caused 7-fold decreased Gpx1 expression in Prdx6-/- mouse lung with no remarkable decrease of Prdx6 expression in Gpx1-/- mice. The percentage of apoptotic cells was significantly increased in AEC II cells from Prdx6-/- mice, and the percentage of AEC II apoptotic cells from Tg Prdx6 kept consistently around 10% under H2O treatments; also, the lipid peroxidation level of AEC II cell membrane was the highest in the group of Prdx6-/- mice, which was about 2 or 4-fold increased compared to the groups of WT or Tg Prdx6, separately; meanwhile, the lipid peroxidation level in Prdx6-/- mice, was also the highest compared to the other groups.

CONCLUSIONSPrdx6 plays a critical role in defending acute oxidative lung injury and its function of defending cell apoptosis and cell membrane lipid peroxidation suggests its unique cell-based protective effect.

Acute Lung Injury ; metabolism ; prevention & control ; Animals ; Antioxidants ; metabolism ; Apoptosis ; Hydrogen Peroxide ; metabolism ; Lipid Peroxidation ; Lung ; drug effects ; metabolism ; Male ; Mice ; Mice, Knockout ; Peroxiredoxin VI ; metabolism

OBJECTIVETo characterize the expressions of peroxiredoxin 1 (Prx1), peroxiredoxin 6 (Prx6) and glial fibrillary acidic protein (GFAP) in human brain astrocytoma and explore their clinical significance.

METHODSThe protein and mRNA expression levels of Prx1, Prx6 and GFAP in human brain astrocytoma and normal brain tissue specimens were determined by Western blotting, RT-PCR and immunohistochemistry.

RESULTSThe protein and mRNA expressions of Prx1 and Prx6 increased significantly in the order of normal brain tissue, grade II astrocytoma, grade III astrocytoma and grade IV astrocytoma (P<0.05). The protein and mRNA expressions of GFAP decreased significantly in grade III and IV astrocytoma compared with those in grade II astrocytoma and normal brain tissues (P<0.05).

CONCLUSIONPrx1 and Prx6 may play important roles in the invasion and malignant development of human brain astrocytoma, and may serve as biomarkers for evaluating the invasiveness, malignancy and prognosis of the tumor as well as potential molecular targets in astrocytoma therapy.

Adolescent ; Adult ; Aged ; Astrocytoma ; metabolism ; pathology ; Brain Neoplasms ; metabolism ; pathology ; Child ; Child, Preschool ; Female ; Glial Fibrillary Acidic Protein ; metabolism ; Humans ; Male ; Middle Aged ; Peroxiredoxin VI ; metabolism ; Peroxiredoxins ; metabolism ; Young Adult

Silicosis is one of the most serious occupational diseases in China and dates back to centuries ago. In this study, we successfully established a rat model of silicosis by intratracheal silica injection for 28 days and determined hydroxyproline levels to evaluate collagen metabolism in lung homogenates. Oxidative stress status was evaluated by detecting catalase and glutathione peroxidase activities. Expression levels of peroxiredoxins (Prx I and Prx VI) were detected by Western blotting. Pulmonary surfactant protein A (SP-A) levels in rat serum and lung tissue were analyzed by ELISA, and SP-A and Prx expression levels in lung tissues were detected by immunohistochemistry. The results suggest that Prx proteins may be involved in pulmonary fibrosis induced by silica. Downregulation of SP-A expression caused due to silica is an important factor in the occurrence and development of silicosis.
Animals ; Disease Models, Animal ; Humans ; Lung ; enzymology ; metabolism ; Male ; Oxidative Stress ; Peroxiredoxin VI ; genetics ; metabolism ; Peroxiredoxins ; genetics ; metabolism ; Pulmonary Surfactant-Associated Protein A ; genetics ; metabolism ; Rats ; Silicon Dioxide ; toxicity ; Silicosis ; genetics ; metabolism