Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin (IL)-8, a C-X-C chemokine, is a potent chemoattractant and an activator for neutrophils, T cells, and other immune cells. The airway and respiratory epithelia play important roles in the initiation and modulation of inflammatory responses via production of cytokines and surfactant. The association between elevated levels of nitric oxide (NO) and IL-8 in acute lung injury associated with sepsis, acute respiratory distress syndrome, respiratory syncytial virus infection in infants, and other inflammatory diseases suggested that NO may play important roles in the control of IL-8 gene expression in the lung. We investigated the role of NO in the control of IL-8 gene expression in H441 lung epithelial cells. We found that a variety of NO donors significantly induced IL-8 mRNA levels, and the increase in IL-8 mRNA was associated with an increase in IL-8 protein. NO induction of IL-8 mRNA was due to increases in IL-8 gene transcription and mRNA stability. NO induction of IL-8 mRNA levels was not inhibited by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and KT-5823, inhibitors of soluble guanylate cyclase and protein kinase G, respectively, and 8-bromo-cGMP did not increase IL-8 mRNA levels. This indicated that NO induces IL-8 mRNA levels independently of changes in the intracellular cGMP levels. NO induction of IL-8 mRNA was significantly reduced by inhibitors of extracellular regulated kinase and protein kinase C. IL-8 induction by NO was also reduced by hydroxyl radical scavengers such as dimethyl sulfoxide and dimethylthiourea, indicating the involvement of hydroxyl radicals in the induction process. NO induction of IL-8 gene expression could be a significant contributing factor in the initiation and induction of inflammatory response in the respiratory epithelium.
Am J Physiol Lung Cell Mol Physiol 2004 Oct
PMID:Nitric oxide increases IL-8 gene transcription and mRNA stability to enhance IL-8 gene expression in lung epithelial cells. 1516 73

To characterize the tachykininergic effects in fire smoke (FS)-induced acute respiratory distress syndrome (ARDS), we designed a series of studies in rats. Initially, 20 min of FS inhalation induced a significant increase of substance P (SP) in bronchoalveolar lavage fluid (BALF) at 1 h and persisted for 24 h after insult. Conversely, FS disrupted 51.4, 55.6, 46.3, and 43.0% enzymatic activity of neutral endopeptidase (NEP, a primary hydrolyzing enzyme for SP) 1, 6, 12, and 24 h after insult, respectively. Immunolabeling density of NEP in the airway epithelium largely disappeared 1 h after insult due to acute cell damage and shedding. These changes were also accompanied by extensive influx of albumin and granulocytes/lymphocytes in BALF. Furthermore, levels of BALF SP and tissue NEP activity dose dependently increased and decreased, respectively, following 0, low (10 min), and high (20 min) levels of FS inhalation. However, neither the time-course nor the dose-response study observed a significant change in the highest affinity neurokinin-1 receptor (NK-1R) for SP. Finally, treatment (10 mg/kg im) with SR-140333B, an NK-1R antagonist, significantly prevented 20-min FS-induced hypoxemia and pulmonary edema 24 h after insult. Further examination indicated that SR-140333B (1.0 or 10.0 mg/kg im) fully abolished early (1 h) plasma extravasation following FS. Collectively, these findings suggest that a combination of sustained SP and NEP inactivity induces an exaggerated neurogenic inflammation mediated by NK-1R, which may lead to an uncontrolled influx of protein-rich edema fluid and cells into the alveoli as a consequence of increased vascular permeability.
Am J Physiol Lung Cell Mol Physiol 2004 Oct
PMID:Substance P and neutral endopeptidase in development of acute respiratory distress syndrome following fire smoke inhalation. 1519 66

1. Florida red tides produce profound neurotoxicity that is evidenced by massive fish kills, neurotoxic shellfish poisoning, and respiratory distress. Red tides vary in potency, potency that is not totally governed by toxin concentration. The purpose of the study was to understand the variable potency of red tides by evaluating the potential for other natural pharmacological agents which could modulate or otherwise reduce the potency of these lethal environmental events. 2. A synaptosome binding preparation with 3-fold higher specific brevetoxin binding was developed to detect small changes in toxin binding in the presence of potential antagonists. Rodent brain labeled in vitro with tritiated brevetoxin shows high specific binding in the cerebellum as evidenced by autoradiography. Synaptosome binding assays employing cerebellum-derived synaptosomes illustrate 3-fold increased specific binding. 3. A new polyether natural product from Florida's red tide dinoflagellate Karenia brevis, has been isolated and characterized. Brevenal, as the nontoxic natural product is known, competes with tritiated brevetoxin for site 5 associated with the voltage-sensitive sodium channel (VSSC). Brevenal displacement of specific brevetoxin binding is purely competitive in nature. 4. Brevenal, obtained from either laboratory cultures or field collections during a red tide, protects fish from the neurotoxic effects of brevetoxin exposure. 5. Brevenal may serve as a model compound for the development of therapeutics to prevent or reverse intoxication in red tide exposures.
Cell Mol Neurobiol 2004 Aug
PMID:Brevenal is a natural inhibitor of brevetoxin action in sodium channel receptor binding assays. 1523 78

The levels of surfactant protein-A (SP-A) and surfactant protein-D (SP-D) in the serum of patients with septic acute respiratory distress syndrome (ARDS) were determined. Patients with sepsis without ARDS were examined as controls. The mean serum SP-A level in the former group was 37.6 +/- 16.2 ng/ml and in the latter group was 31.8 +/- 9.6 ng/ml. The difference between the two groups was not statistically significant. The maximum serum SP-D level was 83.0 +/- 33.9 ng/ml in the control group of patients without ARDS, and 476.3 +/- 391.2 ng/ml in the patients with ARDS. The level in the latter population was significantly higher than that in the former population. No significant correlation was observed between the SP-A and SP-D levels. These results suggest that the serum SP-D levels may serve as a good diagnostic indicator of ARDS in patients with sepsis.
Res Commun Mol Pathol Pharmacol 2002
PMID:Surfactant protein A and D (SP-A, AP-D) levels in patients with septic ARDS. 1524 40

This review will focus on the therapeutic uses of antioxidant liposomes. Antioxidant liposomes have a unique ability to deliver both lipid- and water-soluble antioxidants to tissues. This review will detail the varieties of antioxidants which have been incorporated into liposomes, their modes of administration, and the clinical conditions in which antioxidant liposomes could play an important therapeutic role. Antioxidant liposomes should be particularly useful for treating diseases or conditions in which oxidative stress plays a significant pathophysiological role because this technology has been shown to suppress oxidative stress. These diseases and conditions include cancer, trauma, irradiation, retinotherapy or prematurity, respiratory distress syndrome, chemical weapon exposure, and pulmonary infections.
Mol Biotechnol 2004 Jul
PMID:Therapeutic uses of antioxidant liposomes. 1524 95

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is caused by recessive mutations of the IGHMBP2 gene. The role of IGHMBP2 (immunoglobulin mu-binding protein 2) in the pathomechanism of motor neuron disease is unknown. We have generated antibodies against Ighmbp2 and showed that low levels of Ighmbp2 immunoreactivity are present in the nucleus of spinal motor neurons and high levels in cell bodies, axons and growth cones. Ighmbp2 protein levels are strongly reduced in neuromuscular degeneration (nmd) mice, the mouse model of SMARD1. Mutant mice show severe motor neuron degeneration before first clinical symptoms become apparent. The loss of motor neuron cell bodies in lumbar spinal cord is followed by axonal degeneration in corresponding nerves such as the femoral quadriceps and sciatic nerve and loss of axon terminals at motor endplates. Motor neuron degeneration and clinical symptoms then slowly progress until the mice die at the age of 3-4 months. In addition, myopathic changes seem to contribute to muscle weakness and especially to respiratory failure, which is characteristic of the disorder in humans. Cultured motor neurons from embryonic nmd mice did not show any abnormality with respect to survival, axonal growth or growth cone size, thus differing from motor neurons derived from, e.g. Smn (survival motor neuron) deficient mice, the model of spinal muscular atrophy (SMA). Our data suggest that the pathomechanism in SMARD1 is clearly distinct from other motor neuron diseases such as classic SMA.
Hum Mol Genet 2004 Sep 15
PMID:Characterization of Ighmbp2 in motor neurons and implications for the pathomechanism in a mouse model of human spinal muscular atrophy with respiratory distress type 1 (SMARD1). 1526 81

3-Hydroxy-3-methylglutaric aciduria (OMIM 246450) is an autosomal recessive inborn error of the final step of leucine catabolic and ketogenic pathways, caused by deficiency of the enzyme 3-hydroxy-3-methylglutaryl CoA lyase (HL, HMGCL, EC 4.1.3.4). Clinically, deficiency of the enzyme results in metabolic acidosis, hyperammonemia, and infantile hypoketotic hypoglycaemia usually presenting during the first year of life with vomiting, lethargy, hypotonia, and sometimes with respiratory distress and coma. HL deficiency is relatively common in Arabic populations but seems to be rare in Europe. Our recent experience suggests that HL deficiency is the most frequent organic aciduria in the Portuguese population. We herein report on the molecular study of the HMGCL gene in 11 cases originated from the Northern area of Portugal. We detected the E37X (c.109G > T) mutation, in 84.1% of the alleles, one allele carried the V168fs(-2) (504_505delCT) and other allele the novel D204N (c.610G > A) mutation. The mutation of the last allele remained unidentified. The relatively high frequency of the "common" HMGCL Portuguese mutation makes useful the development of a rapid and specific molecular confirmation of new cases with HL deficiency in our country.
Mol Genet Metab 2004 Aug
PMID:The E37X is a common HMGCL mutation in Portuguese patients with 3-hydroxy-3-methylglutaric CoA lyase deficiency. 1530 32

Adaptation to air breathing at birth is dependent on formation and function of the lung. Lung morphogenesis is a complex process dependent on precise temporal-spatial control of cell proliferation, differentiation and behavior mediated by autocrine-paracrine signaling that instructs transcriptional processes during organogenesis. Mutations in genes causing severe, and often lethal, lung malformations include those in the sonic hedgehog, fibroblast growth factor and thyroid transcription factor-1 pathways. Mutations in genes regulating surfactant homeostasis, necessary for reduction of surface tension in the alveoli, cause lethal respiratory distress at birth or interstitial lung disease in childhood. Inherited disorders of the surfactant system that affect neonatal respiratory adaptation at birth include hereditary surfactant protein B deficiency, mutations in surfactant protein C and the ABCA3 transporter.
Hum Mol Genet 2004 Oct 01
PMID:Genetic disorders influencing lung formation and function at birth. 1535 27

Mutations in Prophet of PIT1 (Prop1), one of several homeodomain transcription factors that are required for the development of the anterior pituitary gland, are the predominant cause of MPHD (multiple pituitary hormone deficiency) in humans. We show that deletion of Prop1 in mice causes severe pituitary hypoplasia with failure of the entire Pit1 lineage and delayed gonadotrope development. The pituitary hormone deficiencies cause secondary endocrine problems and a high rate of perinatal mortality due to respiratory distress. Lung atelectasis in mutants correlates with reduced levels of NKX2.1 and surfactant. Lethality of mice homozygous for either the null allele or a spontaneous hypomorphic allele is strongly influenced by genetic background. Prop1-null mice are an excellent model for MPHD and may be useful for testing the efficacy of pharmaceutical intervention for neonatal respiratory distress.
Hum Mol Genet 2004 Nov 15
PMID:Pituitary hypoplasia and respiratory distress syndrome in Prop1 knockout mice. 1545 76

The transcription factor Nrf2 regulates the basal and inducible expression of numerous detoxifying and antioxidant genes. The cytoplasmic protein Keap1 interacts with Nrf2 and represses its function. Analysis of keap1-knockout mice provides solid evidence that Keap1 acts as a negative regulator of Nrf2 and as a sensor of xenobiotic and oxidative stresses. The simultaneous ablation of the keap1 and nrf2 genes reversed all apparent phenotypes of the Keap1-deficient mice, suggesting that Nrf2 is a primary target of Keap1. The Nrf2-Keap1 system is now recognized as one of the major cellular defence mechanisms against oxidative and xenobiotic stresses. Furthermore, extensive studies have suggested that the Nrf2-Keap1 system contributes to protection against various pathologies, including carcinogenesis, liver toxicity, respiratory distress and inflammation.
Trends Mol Med 2004 Nov
PMID:Nrf2-Keap1 defines a physiologically important stress response mechanism. 1551 81


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>