Search results for " phosphorylation"
showing 10 items of 381 documents
The Role of Transforming Growth Factor-β1 in Airway Inflammation of Childhood Asthma
2013
TGF-beta-targeting structural and inflammatory cells has been implicated in the mechanisms leading to the inflammatory and restructuring processes in asthma, suggesting an impact of TGF-beta1 signaling on the development and persistency of this disease. We investigated the potential early involvement of TGF-beta1 activity in the immunological and molecular mechanisms underlying progression of inflammation in childhood asthma. We evaluated the levels of TGF-beta1 in induced sputum supernatants (ISSs) and the expression of small mother cell against decapentaplegic (Smad) 2 and Smad7 proteins in induced sputum cells (ISCs) from children with intermittent asthma (IA), moderate asthma (MA) and c…
Redox Regulation of Dihydrofolate Reductase: Friend or Troublemaker?
2015
Oxidative stress is a hallmark of cardiovascular diseases1 and a major contributor to vascular dysfunction.2 On the basis on recent concepts, vascular oxidative stress is caused mainly by infiltrating inflammatory cells such as monocytes/macrophages or leucocytes,3,4 producing so-called kindling radicals that lead to the activation of secondary, vascular enzymatic sources of reactive oxygen species (mainly superoxide).2,5 A prominent example is the uncoupled nitric oxide (NO) synthase, which means that an NO-producing antiatherosclerotic enzyme is getting switched to a superoxide-producing proatherosclerotic enzyme.2 Molecular mechanisms causing endothelial NO synthase (eNOS) uncoupling or …
Method for functional study of mitochondria in rat hypothalamus
2008
1872-678X (Electronic) Journal Article Research Support, Non-U.S. Gov't; Different roles of mitochondria in brain function according to brain area are now clearly emerging. Unfortunately, no technique is yet described to investigate mitochondria function in specific brain area. In this article, we provide a complete description of a procedure to analyze the mitochondrial function in rat brain biopsies. Our two-step method consists in a saponin permeabilization of fresh brain tissues in combination with high-resolution respirometry to acquire the integrated respiratory rate of the biopsy. In the first part, we carefully checked the mitochondria integrity after permeabilization, defined exper…
Increased Hypoxic Tolerance by Chemical Inhibition of Oxidative Phosphorylation: “Chemical Preconditioning”
1997
A short ischemic episode preceding sustained ischemia is known to increase tolerance against ischemic cell death. We report early-onset long-lasting neuroprotection against in vitro hypoxia by preceding selective chemical inhibition of oxidative phosphorylation: “chemical preconditioning.” The amplitude of CA1population spikes (psap) in hippocampal slices prepared from control animals (control slices) was 31 ± 27% (mean ± SD) upon 45-min recovery from 15-min in vitro hypoxia. In slices prepared from animals treated in vivo with 20 mg/kg 3-nitropropionate (3-np) 1–24 h prior to slice preparation (preconditioned slices), psap improved to 90 ± 15% (p < 0.01). Posthypoxic oxygen free radical…
Down-regulation of Glutathione and Bcl-2 Synthesis in Mouse B16 Melanoma Cells Avoids Their Survival during Interaction with the Vascular Endothelium
2003
B16 melanoma (B16M) cells with high GSH content show high metastatic activity. However, the molecular mechanisms linking GSH to metastatic cell survival are unclear. The possible relationship between GSH and the ability of Bcl-2 to prevent cell death was studied in B16M cells with high (F10) and low (F1) metastatic potential. Analysis of a Bcl-2 family of genes revealed that B16M-F10 cells, as compared with B16M-F1 cells, overexpressed preferentially Bcl-2 (approximately 5.7-fold). Hepatic sinusoidal endothelium-induced B16M-F10 cytotoxicity in vitro increased from approximately 19% (controls) to approximately 97% in GSH-depleted B16M-F10 cells treated with an antisense Bcl-2 oligodeoxynucl…
Visible light (>395nm) causes micronuclei formation in mammalian cells without generation of cyclobutane pyrimidine dimers
2004
Solar radiation gives rise to DNA damage in mammalian cells not only directly by excitation of DNA, which generates predominantly pyrimidine dimers, but also indirectly by the excitation of endogenous photosensitizers, which causes oxidative DNA modifications. The latter mechanism has a low quantum yield, but it is the only one proceeding in the visible range of the spectrum. To investigate its relevance for the genotoxicity of sunlight, we have analysed the generation of micronuclei associated with the induction of oxidative DNA damage by visible light in melanoma cells and primary human skin fibroblasts. Similar yields of light-induced oxidative DNA base modifications sensitive to the rep…
Assembly of the ribonucleoprotein complex containing the mRNA of the β-subunit of the mitochondrial H+-ATP synthase requires the participation of two…
2002
The mRNA encoding the beta-subunit of the mitochondrial H(+)-ATP synthase (beta-F1-ATPase) is localized in an approx. 150 nm structure of the hepatocyte of mammals. In the present study, we have investigated the cis- and trans-acting factors involved in the generation of the ribonucleoprotein complex containing beta-F1-ATPase mRNA. Two cis-acting elements (beta1.2 and 3'beta) have been identified. The beta1.2 element is placed in the open reading frame, downstream of the region encoding the mitochondrial pre-sequence of the protein. The 3'beta element is the 3' non-translated region of the mRNA. Complex sets of proteins from the soluble and non-soluble fractions of the liver interact with t…
Identification and phenotypic characterization of a subpopulation of T84 human colon cancer cells, after selection on activated endothelial cells
2004
The extravasation of metastatic cells is regulated by molecular events involving the initial adhesion of tumor cells to the endothelium and subsequently the migration of the cells in the host connective tissue. The differences in metastatic ability could be attributed to properties intrinsic of the various primary tumor types. Thus, the clonal selection of neoplastic cells during cancer progression results in cells better equipped for survival and formation of colonies in secondary sites. A cell line (T84SF) exhibiting an altered phenotypic appearance was selected from a colon cancer cell line (T84) by repetitive plating on TNFα-activated human endothelial cells and subsequent selection for…
Metformin increases APP expression and processing via oxidative stress, mitochondrial dysfunction and NF-κB activation: Use of insulin to attenuate m…
2015
AbstractClinical and experimental biomedical studies have shown Type 2 diabetes mellitus (T2DM) to be a risk factor for the development of Alzheimer's disease (AD). This study demonstrates the effect of metformin, a therapeutic biguanide administered for T2DM therapy, on β-amyloid precursor protein (APP) metabolism in in vitro, ex vivo and in vivo models. Furthermore, the protective role of insulin against metformin is also demonstrated. In LAN5 neuroblastoma cells, metformin increases APP and presenilin levels, proteins involved in AD. Overexpression of APP and presenilin 1 (Pres 1) increases APP cleavage and intracellular accumulation of β-amyloid peptide (Aβ), which, in turn, promotes ag…
Fos-related antigen 2 (Fra-2) memorizes photoperiod in the rat pineal gland
2004
As the physiological role of fos-related antigen-2 (Fra-2) is largely unknown and since the pineal plays an important role in the photoperiodic control of the body, we have tested the hypothesis that Fra-2 expression is photoperiod-dependent and may be involved in imprinting photoperiod on the pineal gland and the body as a whole. To this end, we have investigated Fra-2 mRNA expression and Fra-2 protein expression under various light/dark (LD) cycles. A clear nocturnal increase occurs for both monitored parameters under all photoperiodic conditions studied. The level of Fra-2 protein expression clearly depends on photoperiod, because the amount of protein at dark onset and during the night …