Abstract：
:Nitrosamines are carcinogens formed in the mammalian organism from amine precursors contained in food, beverages, cosmetics and drugs. The potent carcinogen, NNK, and the weaker carcinogen, NNN, are nitrosamines formed from nicotine. Metabolites of the nitrosamines react with DNA to form adducts responsible for genotoxic effects. We have identified NNK as a high affinity agonist for the alpha7 nicotinic acetylcholine receptor (alpha7nAChR) whereas NNN bound with high affinity to epibatidine-sensitive nAChRs. Diethylnitrosamine (DEN) bound to both receptors but with lower affinity. High levels of the alpha7nAChR were expressed in human small cell lung cancer (SCLC) cell lines and in hamster pulmonary neuroendocrine cells (PNECs), which serve as a model for the cell of origin of human SCLC. Exposure of SCLC or PNECs to NNK or nicotine increased expression of the alpha7nAChR and caused influx of Ca(2+), activation of PKC, Raf-1, ERK1/2, and c-myc, resulting in the stimulation of cell proliferation. Signaling via the alpha7nAChR was enhanced when cells were maintained in an environment of 10-15% CO(2) similar to that in the diseased lung. Hamsters with hyperoxia-induced pulmonary fibrosis developed neuroendocrine lung carcinomas similar to human SCLC when treated with NNK, DEN, or nicotine. The development of the NNK-induced tumors was prevented by green tea or theophylline. The beta-adrenergic receptor agonist, isoproterenol or theophylline blocked NNK-induced cell proliferation in vitro. NNK and nicotine-induced hyperactivity of the alpha7nAChR/RAF/ERK1/2 pathway thus appears to play a crucial role in the development of SCLC in smokers and could be targeted for cancer prevention.
journal_name
Life Scijournal_title
Life sciencesauthors
Schuller HMdoi
10.1016/j.lfs.2007.03.006subject
Has Abstractpub_date
2007-05-30 00:00:00pages
2274-80issue
24-25eissn
0024-3205issn
1879-0631pii
S0024-3205(07)00255-Xjournal_volume
80pub_type
杂志文章,评审相关文献
LIFE SCIENCES文献大全abstract：:Embryonic heart development is a very complicated process regulated precisely by a network composed of many genes and signaling pathways in time and space. Forkhead box (Fox, FOX) proteins are a family of transcription factors characterized by the presence of an evolutionary conserved "forkhead"or "winged-helix" DNA-b...
journal_title：Life sciences
pub_type： 杂志文章,评审
doi：10.1016/j.lfs.2015.12.001
更新日期：2016-01-01 00:00:00
abstract：:Human uridinediphosphate-glucuronosyltransferase 1A1 (UGT1A1) was expressed in Salmonella typhimurium TA1535 cells by transfection of the cells with plasmids carrying the UGT1A1 cDNA. UGT1A1 cDNA was isolated by a polymerase chain reaction from human liver total RNA and was inserted into the pSE420 plasmid, linked to ...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/s0024-3205(00)00521-x
更新日期：2000-04-07 00:00:00
abstract：:Triiodothyronine (T3) increases phosphoglycerate mutase (PGAM) specific activity in rat skeletal and cardiac muscles. This increase is concomitant with an increase in the proportion of phosphoglycerate mutase isozymes which contain type-M subunit. Propylthiouracil (PTU), an anti-hormone, not only decreases phosphoglyc...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(94)90003-5
更新日期：1994-01-01 00:00:00
abstract：:This study is aimed to investigate the effect of the prolonged intake of conspicuous amounts of licorice (LE), or its natural constituent glycyrrhizin (G) on murine liver CYP-catalyzed drug metabolism. For this purpose the modulation of the regio- and stereo-selective hydroxylation of testosterone, together with the u...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/s0024-3205(97)01154-5
更新日期：1998-01-01 00:00:00
abstract：AIMS:Clinical use of doxorubicin, an effective chemotherapeutic agent, has limited uses due to dose-dependent cardiac toxicity. It has been supposed that the production of free radicals and calcium ions overload can lead to cardiac toxicity. Magnesium is a cardioprotective drug which inhibits lipid peroxidation and red...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2018.06.022
更新日期：2018-08-15 00:00:00
abstract：:The inhibitory activity of methylguanidine, guanidine and their precursors, creatine and creatinine, on both the neuronal constitutive and lung inducible isoforms of nitric oxide synthase were examined in this study. Methylguanidine and guanidine (0.01-3 mM) significantly (P<0.01) inhibited in a concentration-dependen...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/s0024-3205(97)00673-5
更新日期：1997-01-01 00:00:00
abstract：:Hypotensive responses to tryptophan and 5-hydroxytryptophan infusions were studied in normotensive male Sprague-Dawley rats. Results showed that 5-hydroxytryptophan but not tryptophan lowered pressure in a dose dependent way in direct relation to the production of brain serotonin and 5-HIAA. Intrinsic release of serot...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(85)90220-6
更新日期：1985-11-11 00:00:00
abstract：:Cyclic octapeptide analogues of somatostatin (SS) like SMS 201-995 [H-(D) Phe-Cys-Phe-(D) Trp-Lys-Thr-Cys-Thr(ol)] or its Tyr3-derivative 204-090, displaced [125I-Tyr11]-SS 100% from pancreatic membranes but only 62-75% from brain membranes; the remaining sites were displaced by SS. These data indicate that some mini-...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(85)90155-9
更新日期：1985-05-13 00:00:00
abstract：:Different ligands of both the "peripheral" and the "central" benzodiazepine receptors were tested for their ability to induce human monocyte chemotaxis. Only the ligands interacting with the "peripheral receptor" (diazepam and Ro 5-4864) were active, and their action was blocked by the specific antagonist PK 11-195, b...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(93)90275-8
更新日期：1993-01-01 00:00:00
abstract：:Amino acid and reduced glutathione (GSH) levels in substantia nigra (SN) as well as striatal monoamine levels were measured in acetyl-L-carnitine (ALCar) treated and control Swiss-Webster mice. ALCar, L carnitine, or saline were administered i.p. to mice for 5 days and mice were decapitated 24 hours following the last...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(88)90319-0
更新日期：1988-01-01 00:00:00
abstract：:In 6-[18F]fluoro-L-dopa (Fdopa)/positron emission tomography (PET) studies, carbidopa pretreatment increases the Fdopa bioavailability to the brain and enhances the intensity of striatal PET images. Different PET research teams have used various carbidopa doses and routes of administration in non-human primate studies...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(95)00147-x
更新日期：1995-01-01 00:00:00
abstract：:The aim of this study was to investigate whether the A1/A2 receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA), and the selective A1 agonist, N6-cyclopentyladenosine (CPA), induced physical dependence by quantifying specific antagonist-precipitated withdrawal syndromes in conscious rats. In addition, the presence ...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/s0024-3205(01)01155-9
更新日期：2001-07-06 00:00:00
abstract：:Persistent neurochemical changes consistent with parkinsonism have been reported in brains of mice treated with repeated high doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We now report that ethanol or acetaldehyde potentiate MPTP-induced damage to mouse striatum. One hour after the combined treatments...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(87)90030-0
更新日期：1987-03-02 00:00:00
abstract：:Since reduced levels of brain serotonin are known to cause behavioural abnormalities, to which diabetics are also prone, we investigated the effect, in rats, of chronic diabetes on brain serotonin concentration and on the numbers of 5-HT(1A) and 5-HT2 receptors in cerebral cortex and brainstem. Our data show that stre...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/s0024-3205(97)00084-2
更新日期：1997-01-01 00:00:00
abstract：:In some cell systems muscarinic receptor stimulation can induce proliferation or transformation. This phenomenon is subtype-specific (only m1 and m3 receptors are effective) and cell type dependent. In 1321N1 astrocytoma cells activation of m3 receptors stimulates phospholipase C, but does not induce DNA synthesis. In...
journal_title：Life sciences
pub_type： 杂志文章,评审
doi：
更新日期：1997-01-01 00:00:00
abstract：:The nonsteroidal anti-inflammatory drug zomepirac (ZP) is metabolised to a chemically reactive acyl glucuronide conjugate (ZAG) which can form covalent adducts with proteins. In vivo, such adducts could initiate immune or toxic responses. In rats given ZP, the major band detected in liver homogenates by immunoblotting...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/s0024-3205(00)00981-4
更新日期：2001-01-05 00:00:00
abstract：AIMS:Ganoderma lucidum, a traditional Chinese medicine, is well known as a modulator of functions of the immune system as well as an anti-tumour agent. However, its active compounds and their molecular mechanisms of action are not well established. GLIS, a proteoglycan isolated from the fruiting body of G. lucidum, sti...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2010.09.026
更新日期：2010-11-20 00:00:00
abstract：AIMS:Perinatal hypoxic-ischemic insult has acute and long term deleterious effects on many organs including heart. Although tumor necrosis factor alpha (TNF-α) has been reported to increase soon after hypoxia, the inhibition of this mediator has not been documented. The aim of this study was to investigate the effects ...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2012.03.036
更新日期：2012-06-06 00:00:00
abstract：:Testosterone propionate, cortisone, or sesame oil vehicle were given to rats during the last week of pregnancy so that effects of the hormones on anogenital distance, breeding capacity and vaginal opening of the female progeny could be contrasted. Testosterone significantly increased anogenital distance and delayed va...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(92)90248-n
更新日期：1992-01-01 00:00:00
abstract：AIM:This study was undertaken to determine the biological activity of a green tea supplement with respect to cells and erythrocyte membranes and the molecular mechanism of that activity. MAIN METHODS:The extract's activity was evaluated on the basis of its hemolytic, antioxidant and antiinflammatory actions. In additi...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2014.12.025
更新日期：2015-04-01 00:00:00
abstract：:Dialyzed aqueous extracts of plant pollen are widely used in the clinical practice of allergy for diagnostic and therapeutic purposes. The present investigation shows that such allergenic extracts are capable of consuming complement in every human serum, independent of the clinical condition. Complement is engaged by ...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/s0024-3205(97)00101-x
更新日期：1997-01-01 00:00:00
abstract：:Using a specific radioimmunoassay, we measured concentrations of plasma 7B2 (a novel pituitary polypeptide) immunoreactivity (7B2-IR) in normal human subjects, patients with chronic renal failure and those with liver cirrhosis. Mean (+/- SEM) values of plasma 7B2-IR in normal healthy men and women were 55.8 +/- 1.2 pg...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(87)90685-0
更新日期：1987-08-24 00:00:00
abstract：AIMS:Vitamin D is a well-known endocrine regulator of calcium/phosphate homeostasis and has been reported as having a wide range of activities that are potentially beneficial for human health. This study aimed to investigate the effects of pretreatment of vitamin D3 (100, 1000, and 10,000 IU/kg) against lipopolysacchar...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2020.117703
更新日期：2020-07-15 00:00:00
abstract：AIMS:The aim of this study was to evaluate the antinociceptive (acute assays) and anti-inflammatory (chronic assays) effects of kramecyne (KACY), a peroxide isolated from Krameria cytisoides. MAIN METHODS:The antinociceptive activity of KACY was evaluated using the hot plate, acetic acid and formalin tests. The effect...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2014.11.015
更新日期：2015-01-15 00:00:00
abstract：:Guinea pig ileum longitudinal muscle/myenteric plexus preparations contain functional mu- and kappa-opioid receptors. A preparation with blocked kappa receptors was obtained by pretreating guinea pigs with 0.1-10.0 mg/kg intraperitoneal doses of a new kappa-selective affinity label, DIPPA (2-(3,4-dichlorophenyl)-N-met...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/s0024-3205(97)00076-3
更新日期：1997-01-01 00:00:00
abstract：AIMS:The purpose of our investigative work has been to determine whether there can be therapeutic roles in the administration of sildenafil citrate, heparin and several neuropeptides on an animal model where gastric ulcers were induced with acetic acid, and to compare their efficacy. MATERIALS AND METHODS:The animals ...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2017.08.013
更新日期：2017-10-01 00:00:00
abstract：:Based on our earlier animal study, we became interested to investigate if thromboxane A2 (TXA2) is involved in angiotensin converting enzyme (ACE) induced cough in man. To 11 patients with hypertension, who had developed cough induced by ACE inhibitors, a TXA2 synthetase inhibitor, ozagrel was given for 1 to 2 months ...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/s0024-3205(97)00124-0
更新日期：1997-01-01 00:00:00
abstract：:Psychostimulants including amphetamine and cocaine induce locomotion and stereotypy and suppress eating. Although the capacity of cocaine to alter locomotion is usually viewed as related to dopamine neurotransmission, recent studies suggest that norepinephrine, acting through alpha1-adrenergic receptors (alpha1-ARs) c...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2007.08.004
更新日期：2007-09-08 00:00:00
abstract：:Acute post-ischemic cardiac failure was studied in isolated rat hearts. Xylitol, glutamine, aspartic acid and glycine were added during reperfusion, resulting in no inotropic effect. Concanavalin A had a moderate inotropic effect. When concanavalin A added with xylitol, glutamine, aspartic acid and glycine, a rapid re...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(93)90705-8
更新日期：1993-01-01 00:00:00
abstract：:Extracellular phospholipase A2 (PLA2) with proinflammatory activity has recently been discovered in synovial fluids in inflammatory arthritides. In the search for the sources of synovial fluid PLA2, human synovium and articular cartilage were found to contain large quantities of the enzyme. In rheumatoid arthritis (RA...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(91)90381-k
更新日期：1991-01-01 00:00:00
