Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:APRD00369 (ROS)
 19,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has long been thought that the process of bone remodeling is regulated by the chain reactions of bone cells involving chemical mediators, growth factors and synthesis of extracellular matrix proteins etc. In this context, it has also been recognized that physical stimulation is an important factor in the regulation of bone remodeling. Thus, it is vitally important to understand whether the physical stimulation can induce the cellular events regarding autocrine regulation of protein synthesis. This study was conducted to examine the effects of hydrostatic intermittent compressive force (ICF) on the synthesis of the transforming growth factor beta (TGF-beta) and matrix phosphoproteins which may play an important role in the process of bone remodeling. The rat osteosarcoma cells (ROS 17/2.8) were cultured with DMEM containing 10% FCSP. ICF was applied to sub-confluent cells at 130 mb, 15/min cycle for 48h. ICF increased TGF-beta activity of the conditioned medium. This was assessed by its capacity to promote anchorage independent growth of NRK 49F cells and to inhibit the growth of human hepatoma cells (Hep-3B). Furthermore, ICF stimulated the synthesis of the phosphoproteins with Mr. 75 KDa by about 1.4 fold which was visualized by SDS-PAGE on 5-15% gradient gel. Immunoprecipitation of the phosphoproteins with rat osteopontin antibody revealed that the 75 KDa phosphoprotein was identical to osteopontin. The 75 KDa osteopontin synthesis was inhibited by the addition of TGF-beta antibody in a dose dependent manner. These results suggested that ICF stimulated the synthesis of TGF-beta and osteopontin in ROS 17/2.8 cells and that the osteopontin synthesis could be regulated by TGF-beta.
 ...
PMID:[Effects of intermittent compressive force on transforming growth factor beta and osteopontin synthesis in cultured bone cells]. 213 41

Synthesis of metallothionein-I (MT-I) and heme oxygenase mRNAs is rapidly and transiently induced by H2O2 in mouse hepatoma cells (Hepa) and this effect is blocked by catalase. Menadione, which generates free radicals, also induces these mRNAs. Deletion mutagenesis revealed that a region between -42 and -153 in the mouse MT-I promoter was essential for induction of a CAT reporter gene. A multimer of a 16 bp sequence (-101 to -86) that includes an antioxidant response element and overlapping adenovirus major late transcription factor binding site elevated basal expression and allowed induction by H2O2 when inserted upstream of a minimal promoter. However, deletion of this region (-100 to -89) from the intact MT-I promoter (-153) did not completely eliminate response. Multiple copies of a metal response element also permitted response to H2O2. These results suggest that induction of MT-I gene transcription by H2O2 is mediated by at least two different elements within the proximal MT-I gene promoter and suggest a previously undescribed function of the MRE. Induction of MT gene transcription by ROS and the subsequent scavenging of ROS by the MT peptide is reminiscent of the metal regulatory loop and is consistent with the hypothesized protective functions of MT.
 ...
PMID:Transcriptional induction of the mouse metallothionein-I gene in hydrogen peroxide-treated Hepa cells involves a composite major late transcription factor/antioxidant response element and metal response promoter elements. 780 Apr 94

PTH is a mediator of skeletal development and remodeling that influences gene expression in osteoblastic cells. It is well established that PTH modulates the activity of membrane-associated second messenger signal transduction pathways. In these studies we have addressed the potential contribution of components of cell structure to the integration of PTH-related regulatory signals that influence the expression of bone cell genes. Chronic treatment of ROS 17/2.8 rat osteosarcoma cells with PTH is accompanied by changes in gene expression that are at least in part transcriptionally controlled. To explore the involvement of nuclear architecture in PTH-responsive modifications in gene expression, we investigated changes in the nuclear matrix after PTH treatment. Consistent with a role for the nuclear matrix in determining spatial organization and topology of chromatin as well as in the localization and targeting of transcription factors, we observed PTH-associated changes in a 200-kilodalton nuclear matrix protein in response to PTH. A significant down-regulation of synthesis was observed when nuclear matrix proteins were resolved electrophoretically in two-dimensional gels. This protein was restricted to the nuclear matrix and was not detected in the chromatin or cytoskeletal cellular fractions. These alterations in nuclear matrix proteins that occur after PTH treatment in osteosarcoma cells were phenotype related. They did not occur in UMR-106 POL or H4 hepatoma cells. Our findings support a role for the nuclear matrix in transducing PTH-mediated regulatory signals to facilitate the extent to which genes in osteoblasts are transcribed.
 ...
PMID:Parathyroid-responsive modifications in the nuclear matrix of ROS 17/2.8 rat osteosarcoma cells. 813 38

A well differentiated human hepatoma cell line (Hep G2) was used to explore potential roles for PTH-related peptide (PTHrP) as an autocrine/paracrine growth factor. Using Northern analysis or reverse transcription-PCR, Hep G2 cells were found to express messenger RNAs for both PTHrP and the cloned PTH/PTHrP receptor, and the cells exhibited specific binding for [125I]PTHrP(1-36). Hep G2 growth medium was found to contain relatively large amounts of immunoreactive PTHrP (30 vs. 1-2 pM in medium not exposed to cells), and the PTHrP in growth medium (conditioned medium) was shown to contain N-terminal PTHrP biological activity, as assessed by the ability of the medium to stimulate cAMP production in rat osteosarcoma cells (ROS 17/2.8). Conditioned medium produced a dose-dependent severalfold increase in ROS cell cAMP that could be blocked by the PTHrP receptor antagonist [Asn10,Leu11,DTrp12]PTHrP-(7-34). PTHrP in Hep G2 cells also was detected by immunocytochemistry using antiserum to either synthetic PTHrP-(1-34) or recombinant PTHrP-(-5 to 139). Furthermore, these antisera were found to inhibit the ability of PTHrP-(1-34) to stimulate ROS cell cAMP production. When either antiserum (1:800-1:100 dilution) was added to subconfluent Hep G2 cells in medium containing 5% FBS for 3 days, a dose-related 40-50% increase in cell number occurred that could be inhibited by concurrent addition of 10 microM synthetic PTHrP-(1-36). The results show that Hep G2 cells synthesize and secrete both immunoreactive and biologically active PTHrP. As neutralization of PTHrP secreted by these cells by the addition of antiserum to PTHrP resulted in increased cell growth, the findings suggest that PTHrP can function as an autocrine or paracrine growth factor to suppress the growth of these human hepatoma cells.
 ...
PMID:Effect of endogenously produced parathyroid hormone-related peptide on growth of a human hepatoma cell line (Hep G2). 864 Nov 88

Parathyroid hormone (PTH) alters osteoblast morphology. How these changes in cell shape modify nuclear structure and ultimately gene expression is not known. Chronic exposure to rat PTH (1-34) [10 nM] attenuated the expression of 200, 190, and 160 kD proteins in the nuclear matrix-intermediate filament subfraction of the rat osteosarcoma cells, ROS 17/2.8 [Bidwell et al. (1994b): Endocrinology 134:1738-1744]. Here, we determined that these same PTH-responsive proteins were expressed in rat metaphyseal osteoblasts. We identified the 200 kD protein as a non-muscle myosin. Although the molecular weights, subcellular distribution, and half-lives of the 190 and 160 kD proteins were similar to topoisomerase II-alpha and -beta, nuclear matrix enzymes that mediate DNA topology, the 190 and 160 kD proteins did not interact with topoisomerase antibodies. Nevertheless, the expression of topoisomerase II-alpha, and NuMA, a component of the nuclear core filaments, was also regulated by PTH in the osteosarcoma cells. The 190 kD protein was selectively expressed in bone cells as it was not observed in OK opossum kidney cells, H4 hepatoma cells, or NIH3T3 cells. PTH attenuated mRNA expression of the PTH receptor in our cell preparations. These results demonstrate that PTH selectively alters the expression of osteoblast membrane, cytoskeletal, and nucleoskeletal proteins. Topoisomerase II-alpha, NuMA, and the 190 and 160 kD proteins may direct the nuclear PTH signalling pathways to the target genes and play a structural role in osteoblast gene expression.
 ...
PMID:Parathyroid hormone regulates the expression of rat osteoblast and osteosarcoma nuclear matrix proteins. 891 89

Liver damage ranges from acute hepatitis to hepatocellular carcinoma, through apoptosis, necrosis, inflammation, immune response, fibrosis, ischemia, altered gene expression and regeneration, all processes that involve hepatocyte, Kupffer, stellate, and endothelial cells. Reactive oxygen and nitrogen species (ROS, RNS) play a crucial role in the induction and in the progression of liver disease, independently from its etiology. They are involved in the transcription and activation of a large series of cytokines and growth factors that, in turn, can contribute to further production of ROS and RNS. The main sources of free radicals are represented by hepatocyte mitochondria and cytochrome p450 enzymes, by endotoxin-activated macrophages (Kupffer cells), and by neutrophils. The consequent alteration of cellular redox state is potentiated by the correlated decrease of antioxidant and energetic reserves. Indices of free radical-mediated damage, such as the increase of malondialdehyde, 4-hydroxynonenal, protein-adducts, peroxynitrite, nitrotyrosine, etc., and/or decrease of glutathione, vitamin E, vitamin C, selenium, etc., have been documented in patients with viral or alcoholic liver disease. These markers may contribute to the monitoring the degree of liver damage, the response to antiviral therapies and to the design of new therapeutic strategies. In fact, increasing attention is now paid to a possible "redox gene therapy." By enhancing the antioxidant ability of hepatocytes, through transgene vectors, one could counteract oxidative/nitrosative stress and, in this way, contribute to blocking the progression of liver disease.
 ...
PMID:Oxidative stress in viral and alcoholic hepatitis. 1249 74

Aflatoxin B(1) (AFB(1)) causes oxidative stress and ROS formation via metabolic activation of AFB(1). Glycyrrhizic acid (GA) has been reported to have antioxidative properties. The present study was to investigate the effect of GA, a major component of licorice on AFB(1)-induced cytotoxicity in human hepatoma cell line (HepG2). GA displayed protective effects against AFB(1) treatment. Both CYP1A1, and glutathione S-transferase (GST) activities were increased in cells after treatment with the GA, while CYP1A2 did not seem to be affected by GA. For cells without GA pre-treatment, cell injury was implicated as indicated by the decrease in cell viability. The time-course study of GA showed pretreatment of cells with GA for 24 h was effective. The treatment of cells with GA and AFB(1) enhanced the detoxifying enzyme activity. The pre-treatment of cells with GA provides protective effects in terms of the enzyme activity and increase in cell viability. The results suggest that GA protects against aflatoxin-induced oxidative stress. This may contribute to its anticarcinogenic capability. The protective effect is likely due to its capacity to inhibit the metabolic activation of hepato-toxin, a critical factor in the pathogenesis of chemical-induced carcinogenicity.
 ...
PMID:Inhibition of glycyrrhizic acid on aflatoxin B1-induced cytotoxicity in hepatoma cells. 1276 92

We have shown that mitochondrial DNA-depleted (rho(0)) SK-Hep1 hepatoma cells are resistant to apoptosis, contrary to previous papers reporting normal apoptotic susceptibility of rho(0) cells. We studied the changes of gene expression in SK-Hep1 rho(0) cells. DNA chip analysis showed that MnSOD expression was profoundly increased in rho(0) cells. O(2)(.) contents increased during rho(0) cell derivation but became normalized after establishment of rho(0) phenotypes, suggesting that MnSOD induction is an adaptive process to increased O(2)(.). rho(0) cells were resistant to menadione, paraquat, or doxorubicin, and O(2)(.) contents after treatment with them were lower in rho(0) cells compared with parental cells because of MnSOD overexpression. Expression levels and activity of glutathione peroxidases were also increased in rho(0) cells, rendering them resistant to exogenous H(2)O(2). rho(0) cells were resistant to p53, and intracellular ROS contents after p53 expression were lower compared with parental cells. Other types of rho(0) cells also showed increased MnSOD expression and resistance against ROS. Heme oxygenase-1 expression was increased in rho(0) cells, and a heme oxygenase-1 inhibitor decreased the induction of MnSOD in rho(0) cells and their resistance against ROS donors. These results indicate that rho(0) cells are resistant to cell death contrary to previous reports and suggest that an adaptive increase in the expression of antioxidant enzymes renders cancer cells or aged cells with frequent mitochondrial DNA mutations to resist against oxidative stress, host anti-cancer surveillance, or chemotherapeutic agents, conferring survival advantage on them.
 ...
PMID:Resistance of mitochondrial DNA-depleted cells against cell death: role of mitochondrial superoxide dismutase. 1466 Jun 25

Apoptosis and necrosis are distinct forms of cell death that occur in response to various agents. We studied the action of N-Acetyl-D-sphingosine (C2-ceramide) or N-hexanoyl-D-sphingosine (C6-ceramide) in human hepatoma HepG2 cell line. The cells were treated in vitro for 1-24 h. Cell toxicity was evaluated by MTT assay. DNA content was estimated by gel electrophoresis and flow cytometry. Measurement of mitochondrial respiration, analysis of cytochrome c release and caspase-3 activation were assessed in order to determine if either of these events in the induction of apoptosis and/or necrosis was predominant. We have demonstrated that C2 and C6-ceramide were cytotoxic in a time and dose-dependent manner. After 24 h of treatment with 100 microM of C2 and C6 the morphology (May-Giemsa staining) of treated cells displayed an apoptotic phenotype in C6-treated cells, confirmed by a high (sub-G1 peak > 20%) proportion by flow cytometry while a necrotic morphology was observed after C2-ceramide treatment, confirmed by DNA smearing in DNA electrophoresis. After C6-ceramide incubation, the respiratory chain was functional only slightly inhibited (20%), there was production of ATP, cytochrome c release without ROS production, activation of caspase-3 and induction of apoptosis. On the contrary, C2-ceramide inhibited the respiratory chain more intensely (80%) increased significantly ROS production, which resulted in an arrest of ATP production, no cytochrome c release and absence of caspase-3 activation. Finally after complete exhaustion of intracellular ATP, mitochondrial explosion induced necrotic cell death. In conclusion, evidence suggest that mitochondrial respiratory chain function is essential for controlling the decision of the cell to enter a apoptotic or necrosis process.
 ...
PMID:Commitment to apoptosis by ceramides depends on mitochondrial respiratory function, cytochrome c release and caspase-3 activation in Hep-G2 cells. 1467 99

Physalis angulata and P. peruviana are herbs widely used in folk medicine. In this study, the aqueous and ethanol extracts prepared from the whole plant of these species were evaluated for their antihepatoma activity. Using XTT assay, three human hepatoma cells, namely Hep G2, Hep 3B and PLC/PRF/5 were tested. The results showed that ethanol extract of P. peruviana (EEPP) possessed the lowest IC50 value against the Hep G2 cells. Interestingly, all extracts showed no cytotoxic effect on normal mouse liver cells. Treatment with carbonyl cyanide m-chlorophenyl hydrazone, a protonophore, caused a reduction of membrane potential (Deltapsim) by mitochondrial membrane depolarization. At high concentrations, EEPP was shown to induce cell cycle arrest and apoptosis through mitochondrial dysfunction as demonstrated by the following observations: (i) EEPP induced the collapse of Deltapsim and the depletion of glutathione content in a dose dependent manner; (ii) pretreatment with the antioxidant (1.0 microg/ml vitamin E) protected cells from EEPP-induced release of ROS; and (iii) at concentrations 10 to 50 microg/ml, EEPP displayed a dose-dependent accumulation of the Sub-G1 peak (hypoploid) and caused G0/G1-phase arrest. Apoptosis was elicited when the cells were treated with 50 microg/ml EEPP as characterized by the appearance of phosphatidylserine on the outer surface of the plasma membrane. The results conclude that EEPP possesses potent antihepatoma activity and its effect on apoptosis is associated with mitochondrial dysfunction.
 ...
PMID:Antihepatoma activity of Physalis angulata and P. peruviana extracts and their effects on apoptosis in human Hep G2 cells. 1496


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