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At least 631 records · Page 35Linked to original sources

PubMed2002

Prevention of cellular ROS damage by isovitexin and related flavonoids.

The antioxidant properties of isovitexin and related flavonoids were studied. Isovitexin inhibited xanthine oxidase with an IC50 value of = 15.2 microM. The flavonoid analogues, apigenin, kaempferol, quercetin, myricetin, and genistein also inhibited xanthine oxidase with IC50 values of 0.58, 2.18, 1.09, 9.90, and 4.83 microM, respectively. Isovitexin protected DNA from the Fenton reaction-induced breakage in a dose-dependent manner with an IC50 value of 9.52 microM. Isovitexin also protected HL-60 cells from the ROS damage induced by the xanthine/xanthine oxidase reaction. Isovitexin exhibited the lowest cytotoxicity toward HL-60 cells (LD50 >400 microM) compared to the other flavonoids examined. In addition, excess hydrogen peroxide induced by cadmium in A2780 ovarian cells was significantly suppressed by isovitexin. These results suggest that isovitexin in rice may protect cells from oxidative stress.

Apigenin↗

PubMed1987

Heterologous transmembrane signaling by a human insulin receptor-v-ros hybrid in Chinese hamster ovary cells.

A hybrid receptor molecule composed of the extracellular ligand-binding domain of the human insulin receptor and the transmembrane and cytoplasmic (protein-tyrosine kinase) domains of the chicken sarcoma virus UR2 transforming protein p68gag-ros has been constructed and expressed in Chinese hamster ovary (CHO) cells. The hybrid is processed normally into alpha and hybrid beta subunits, is expressed on the cell surface at high levels, and binds insulin with near-wild-type affinity. Furthermore, insulin stimulates the phosphorylation on tyrosine residues of the hybrid beta subunit in vivo and the phosphorylation of an exogenous substrate [poly(Glu,Tyr)] in vitro. Thus the hybrid is capable of heterologous transmembrane signaling. However, the hybrid mediates neither the insulin-activated uptake of 2-deoxyglucose nor the incorporation of [3H]thymidine into DNA, suggesting that the physiological response(s) mediated by ligand-activated protein-tyrosine kinases may utilize distinct intracellular mechanisms for postreceptor signaling.

Animals↗

PubMed1997

Stimulation by 1alpha,25(OH)2-vitamin D3 of whole cell chloride currents in osteoblastic ROS 17/2.8 cells. A structure-function study.

1alpha,25-Dihydroxyvitamin D3 (1alpha,25(OH)2D3) can generate biological responses via genomic and nongenomic mechanisms. This article reports for the first time the effects of 1alpha,25(OH)2D3 and structurally related analogs on whole cell chloride currents in osteoblastic cells. 1alpha,25(OH)2D3 promoted the rapid enhancement of outwardly rectifying Cl- currents in 93% of the osteoblasts in a concentration-dependent manner, with a maximal increase of about 4-fold between 0.5 and 5 nM. This effect of 1alpha,25(OH)2D3 was blocked by 1 nM stereoisomer 1beta,25(OH)2D3 when added to the bath before 1alpha,25(OH)2D3. On the other hand, 1 nM of the 6-s-cis locked analog 1alpha,25(OH)2-lumisterol3 significantly increased by about 2.2-fold outward Cl- currents in the ROS 17/2.8 cells, whereas the increase promoted by same concentration of the 6-s-trans locked analog 1alpha,25(OH)2-tachysterol (0.8-fold) was significantly lower, suggesting that the 6-s-cis locked or steroid-like form was preferred over the extended 6-s-trans conformer to promote these rapid effects of the hormone. We conclude that the agonist effects of 1alpha,25(OH)2D3 in osteoblasts at the cellular membrane level seem to be determined by some structural features of the molecule which may be crucial for its interaction with a putative membrane receptor in the cell surface.

Calcitriol↗

PubMed2001

Calcium spiking activity and baseline calcium levels in ROS 17/2.8 cells exposed to extremely low frequency electromagnetic fields (ELF EMF).

PURPOSE: To determine whether extremely low frequency electromagnetic fields can alter average free cytosolic calcium ion concentrations [Ca2+]i and transient increases in [Ca2+]i in populations of ROS 17/2.8 cells. MATERIALS AND METHODS: Cells loaded with the calcium-selective luminescent photoprotein, aequorin, were placed in the bottom of a sample chamber, which was inserted into the gap of a previously described air gap reactor system where they were exposed either to sinusoidal magnetic fields at a variety of frequencies and flux densities or to sham conditions. Real-time recordings of photon counts due to aequorin luminescence were obtained and data were analysed with the use of probit plots. RESULTS: Probit plots of data obtained from cells exposed to the various magnetic fields were virtually superimposable over the data obtained for the same cultures during pre- and post-exposure sham or no-field periods. CONCLUSION: These experiments provided no evidence for any effects of ELF EMF, either positive or negative, on either average [Ca2+]i or on transient increases in [Ca2+]i.

Aequorin↗

PubMed2006

ROS and protein oxidation in early stages of cytotoxic drug induced apoptosis.

Cytotoxic drugs induce cell death through induction of apoptosis. This can be due to activation of a number of cell death pathways. While the downstream events in drug induced cell death are well understood, the early events are less clear. We therefore used a proteomic approach to investigate the early events in apoptosis induced by a variety of drugs in HL60 cells. Using 2D-gel electrophoresis, we were able to identify a number of protein changes that were conserved between different drug treatments. Identification of post-translational modifications (PTM) responsible for these proteome changes revealed an increase in protein oxidation in drug treated cells, as well as changes in protein phosphorylation. We demonstrate an accumulation of oxidised proteins within the ER, which lead to ER stress and calcium release and may result in the induction of apoptosis. This study demonstrates the importance of ROS mediated protein modifications in the induction of the early stages of apoptosis in response to chemotherapeutic drug treatment.

Antineoplastic Agents↗

PubMed2007

Synthesis and ESR studies of a novel cyclic nitrone spin trap attached to a phosphonium group-a suitable trap for mitochondria-generated ROS?

In this study we report the synthesis and biological application of a novel cyclic nitrone spin trap containing a phosphonium cation. This new spin trap ([4-(2-methyl-1-oxy-3, 4-dihydro-2H-pyrrole-2-carbonyloxy)-butyl]-triphenyl-phosphonium bromide, MitoBMPOBr) is a derivative of the cyclic nitrone, 5-tert-butoxycarbonyl 5-methyl-1-pyrroline N-oxide (BMPO). MitoBMPOBr forms radical adducts upon trapping of superoxide and hydroxyl radicals that exhibit highly distinct and characteristic EPR spectra. The stability of these adducts is comparable to those of BMPO. Because of the presence of a positively-charged phosphonium moiety, MitoBMPOBr may be suitable for trapping reactive oxygen species (ROS) in the mitochondria.

Mitochondria↗

PubMed2006

Impact of ROS on ageing of two fungal model systems: Saccharomyces cerevisiae and Podospora anserina.

To provide a foundation for the development of effective interventions to counteract various age-related diseases in humans, ageing processes have been extensively studied in various model organisms and systems. However, the mechanisms underlying ageing are still not unravelled in detail in any system including rather simple organisms. In this article, we review some of the molecular mechanisms that were found to affect ageing in two fungal models, the unicellular ascomycete Saccharomyces cerevisiae and the filamentous ascomycete Podospora anserina. A selection of issues like retrograde response, genomic instability, caloric restriction, mtDNA reorganisation and apoptosis is presented and discussed with special emphasis on the role reactive oxygen species (ROS) play in these diverse molecular pathways.

Animals↗

PubMed1997

The role of reactive oxygen species (ROS) in the effector mechanisms of human antimycobacterial immunity.

The aim of this study was to determine the role of reactive oxygen species (ROS) in checking the growth of intracellular mycobacteria within human phagocytes. Peripheral blood-derived neutrophils and monocyte-derived macrophages were isolated from Chronic Granulomatous Disease (CGD) patients and normal healthy human volunteers. CGD patients are known to have a defect in the NADPH oxidase pathway, resulting in their neutrophils and monocyte-derived macrophages being unable to generate oxygen radicals which are required to kill intracellular bacteria. The cells were then infected with Bacille Calmette Guerin (BCG) or Mycobacterium avium, and the bacterial growth in each cell type determined by Colony Forming Units (CFU) estimate. The results obtained indicate that there was no demonstrable inhibition in the intracellular mycobacterial growth within neutrophils or macrophages derived from either Chronic Granulomatous Disease (CGD:deficient in NADPH oxidase pathway) or normal healthy volunteers. Macrophage treatment with either IFN-gamma or TNF-alpha had no effect.

Cells, Cultured↗

PubMed1998

Regulation of the transcription of parathyroid-hormone/parathyroid-hormone-related peptide receptor mRNA by dexamethasone in ROS 17/2.8 osteosarcoma cells.

Previous studies have shown that dexamethasone enhanced the expression of parathyroid-hormone/parathyroid-hormone-related peptide (PTH/ PTHrP) receptor mRNA in ROS 17/2.8 osteosarcoma cells. The aim of this study was to determine whether the induction of PTH/PTHrP receptor expression in such osteoblast-like cells is regulated at the gene level. Dexamethasone increased the steady-state levels of PTH/PTHrP receptor mRNA twofold at 6 h, and nearly threefold at 24 h. The half-life of the PTH/PTHrP receptor mRNA, in the presence of actinomycin D, was 6 h both in untreated and in dexamethasone-treated cells. When measured by nuclear run-on assay, the rate of PTH/PTHrP receptor gene transcription was increased twofold at 24 h. PTH/PTHrP receptor mRNA expression was blocked completely after 24 h of treatment with cycloheximide. The binding of PTH/PTHrP to their receptor required the synthesis of new protein and was shown to be specifically dependent on the interaction of dexamethasone with the glucocorticoid receptor. These data indicate that the enhancing effect of dexamethasone on PTH/PTHrP receptor expression is rapid, requires de novo protein synthesis, and increases the transcription rate of the PTH/PTHrP receptor gene.

Animals↗

PubMed2003

Arabidopsis NDK1 is a component of ROS signaling by interacting with three catalases.

Plants sense various environmental stimuli and have specific signaling pathways to respond to these cues. We focused on light responsive components and found that NDKs were phosphorylated specifically after red light irradiation in Pisum sativum [Tanaka et al. (1998) J. Photochem. Photobiol. B 45: 113] and after blue light irradiation in Neurospora crassa [Oda and Hasunuma (1997) Mol. Gen. Genet. 256: 593, Ogura et al. (2001) J. Biol. Chem. 276: 21228]. We performed yeast two-hybrid screening using AtNDK1, the counterpart of NDK-P1 (Pisum sativum NDK1) in Arabidopsis, as bait, and isolated catalase3 (AtCat3). Interactions between AtNDK1-AtCAT1 and AtNDK1-AtCAT2 were also detected with the two-hybrid system. Non-denaturing two-dimensional gel electrophoresis of crude extracts from plants revealed that catalase and NDK activities co-migrated in the same area of the gel. Transgenic plants expressing AtNDK1 under control of the CaMV 35S promoter exhibited tolerance to paraquat and high ability to eliminate exogenous H2O2. These results indicate that AtNDK1 has a role in ROS response.

Arabidopsis↗

PubMed1999

Infertile spermatozoa of c-ros tyrosine kinase receptor knockout mice show flagellar angulation and maturational defects in cell volume regulatory mechanisms.

Homozygous c-ros knockout male mice that lack prepubertal differentiation of the epididymal initial segment are healthy but sterile, despite normal sperm production and mating. Detailed computerized analysis of the motility of spermatozoa maturing in the epididymis revealed only minor defects. However, the majority of motile mature sperm released from the cauda epididymidis showed various extents of flagellar angulation that could not be corrected by raising extracellular osmolality. Measurement of the osmolality of cauda epididymal fluid showed no difference from the wild type. Studies in wild-type mice indicated a maturational change in the ability of motile sperm to maintain straight flagella during incubation, but angulation was induced in cauda sperm by the volume-sensitive ion channel blockers quinine, 5-nitro-2-(3-phenylpropylamino)-benzoic acid and BaCl(2), or by exposure to hypotonic media. Flagellar angulation, induced in the wild type or intrinsic to the knockout, was relieved upon demembranation by Triton X-100, confirming that it was a cell swelling phenomenon. A lack of response of immature wild-type sperm and mature knockout sperm to the channel blockers suggests that there is normally a development of the volume regulatory mechanisms upon maturation that is defective in sperm from the knockout animal. The resultant flagellar angulation may account for the reduction in sperm numbers in the oviduct of mated females and the failure to fertilize in vivo.

Animals↗

PubMed2003

Protein kinase C-dependent increase in reactive oxygen species (ROS) production in vascular tissues of diabetes: role of vascular NAD(P)H oxidase.

Hyperglycemia seems to be an important causative factor in the development of micro- and macrovascular complications in patients with diabetes. Several hypotheses have been proposed to explain the adverse effects of hyperglycemia on vascular cells. Both protein kinase C (PKC) activation and oxidative stress theories have increasingly received attention in recent years. This article shows a PKC-dependent increase in oxidative stress in diabetic vascular tissues. High glucose level stimulated reactive oxygen species (ROS) production via a PKC-dependent activation of NAD(P)H oxidase in cultured aortic endothelial cells, smooth muscle cells, and renal mesangial cells. In addition, expression of NAD(P)H oxidase components were shown to be upregulated in vascular tissues and kidney from animal models of diabetes. Furthermore, several agents that were expected to block the mechanism of a PKC-dependent activation of NAD(P)H oxidase clearly inhibited the increased oxidative stress in diabetic animals, as assessed by in vivo electron spin resonance method. Taken together, these findings strongly suggest that the PKC-dependent activation of NAD(P)H oxidase may be an essential mechanism responsible for increased oxidative stress in diabetes.

Animals↗

PubMed1992

The role of iron in an acute model of skin inflammation induced by reactive oxygen species (ROS).

The effect of iron was studied in rats in a ROS-initiated model of acute skin inflammation. Iron dextran was administered i.v. 24 h before the induction of the inflammatory response by intradermal injection of glucose oxidase attached to polyethylene glycol (GOD-PEG). Iron exacerbated the response at 24 and 48 h (P greater than 0.001). Histologically, a similar picture was seen to that without iron except for an increase in tissue oedema and matrix destruction including the skin glands. Associated with iron loading was an increase in Perls stainable iron in the skin (P greater than 0.025) and liver (P greater than 0.001). However, skin inflammation without iron loading also increased skin iron levels (P greater than 0.025). Total serum iron was decreased in iron-loaded and GOD-PEG animals (P greater than 0.01) and the unbound iron binding capacity (UIBC) increased (P greater than 0.01).

Animals↗

PubMed1991

Two point mutations in the transmembrane domain of P68gag-ros inactive its transforming activity and cause a delay in membrane association.

The transforming protein of the avian sarcoma virus UR2 is a 68-kDa transmembrane tyrosine protein kinase. We examined the relationship between membrane localization and transforming activity of P68 by changing Val-168-Val-169 in its hydrophobic domain into Asp-168-Glu-169. The resulting transmembrane (TM) mutant (P68TM) lost transforming activity toward chicken embryo fibroblasts (CEF). We found that the mutant protein was expressed and rapidly degraded into a smaller form which was still membrane associated and kinase active. The instability of the TM mutant protein is a phenomenon only manifested in CEF, because the same mutant protein was expressed with efficiency and stability similar to those of the wild-type protein in a transient expression system in COS cells. However, there are several differences between the wild-type and the TM mutant proteins in COS cells. The wild-type protein is more heavily phosphorylated and associated with membrane fractions in a cotranslational manner. It is enzymatically active when recovered from membrane fractions. The TM mutant protein is less phosphorylated, more labile toward protease degradation, and delayed in membrane association, with a lag period of 30 min or longer, and has little kinase activity when recovered from membrane fractions. Most of the kinase-active TM mutant protein was found in the cytosol fractions. Despite the delay, most of the TM protein in COS cells was found to be membrane associated, and its orientation on the cell surface was similar to that of the wild-type protein. It is probable that loss of the CEF-transforming activity of the TM mutant protein is due to its susceptibility to protease degradation resulting from improper membrane association of the newly synthesized product. The differences in the kinetics of membrane association and the distribution of kinase activity in COS cells might not be directly applicable in explaining the inability of the TM mutant to transform CEF but are intriguing as regards protein biosynthesis and translocation. The difference between CEF and COS cells implies that different factors or pathways are involved in the biosynthesis and processing of the TM mutant protein in these two cellular environments. Changes of P68TM in the kinetics of membrane association indicate that the transmembrane domain of ros, besides functioning as a membrane anchor, also plays a role in directing initial membrane association.

Animals↗

PubMed1992

Dose-dependent effects of aluminum on osteocalcin synthesis in osteoblast-like ROS 17/2 cells in culture.

This in vitro study evaluates the effect of aluminum (Al3+) on osteocalcin, a small protein that is produced by the osteoblast. After stimulation with various doses of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3; 10(-11) to 10(-9) M], osteocalcin was consistently lower in the culture medium of ROS 17/2 osteoblastic cells conditioned with 5 microM Al(3+)-saturated transferrin (AlTR) than in apotransferrin (ApoTR)-treated controls. In a second experiment, cultures were conditioned with various doses of AlTR or ApoTR (1.6-8.0 microM) and stimulated with 10(-9) M 1,25(OH)2D3. High doses of AlTR (4.8-8.0 microM) resulted in lower medium and unchanged intracellular content of osteocalcin than treatment with equal amounts of ApoTR. However, in the same experiment, lower doses of AlTR or ApoTR (1.6 and 3.2 microM) yielded different results, i.e., increased medium and intracellular contents of osteocalcin in the Al(3+)-treated cells. Expression of osteocalcin mRNA was not altered in cultures conditioned with low (1.6 microM) or high (8.0 microM) concentrations of AlTR or ApoTR. Similarly, no effect of Al3+ was observed on total protein content, the rate of total protein synthesis, and the degradation of secreted osteocalcin in cultures conditioned with various doses of AlTR or ApoTR. These findings suggest that AlTR affects osteocalcin synthesis in a specific manner, without concomitant effects on the rate of total protein synthesis or on the rate of degradation of osteocalcin. This effect is dose dependent, i.e., low doses of AlTR stimulate and high doses suppress osteocalcin synthesis and/or secretion, and it appears to be posttranscriptional, since the expression of osteocalcin mRNA is not affected.

Aluminum↗

PubMed2006

Mechanisms of Liver Injury. I. TNF-alpha-induced liver injury: role of IKK, JNK, and ROS pathways.

TNF-alpha activates several intracellular pathways to regulate inflammation, cell death, and proliferation. In the liver, TNF-alpha is not only a mediator of hepatotoxicity but also contributes to the restoration of functional liver mass by driving hepatocyte proliferation and liver regeneration. This review summarizes recent advances in TNF-alpha signaling mechanisms that demonstrate how the IKK, ROS, and JNK pathways interact with each other to regulate hepatocyte apoptosis and proliferation. Activation of these pathways is causatively linked to liver injury induced by concanavalin A, TNF-alpha, and ischemia-reperfusion and to liver regeneration and hepatocarcinogenesis. In light of recent findings, pharmacological inhibitors of JNK and IKK and antioxidants may be promising new tools for the treatment of hepatitis, ischemia-reperfusion injury, and hepatocellular carcinoma.

Animals↗

PubMed2004

EGFR-independent activation of p38 MAPK and EGFR-dependent activation of ERK1/2 are required for ROS-induced renal cell death.

2,3,5-Tris-(glutathion-S-yl)hydroquinone (TGHQ), a reactive metabolite of the nephrotoxicant hydroquinone, induces the ROS-dependent activation of MAPKs, followed by histone H3 phosphorylation and oncotic cell death in renal proximal tubule epithelial cells (LLC-PK(1)). Cell death and histone H3 phosphorylation are attenuated by pharmacological inhibition of p38 MAPK or ERK1/2 pathways. Because TGHQ, but not epidermal growth factor (EGF), induces histone H3 phosphorylation and cell death in LLC-PK(1) cells, we hypothesized that there are differences in the mechanisms by which TGHQ and EGF induce activation of the EGF receptor (EGFR). We therefore compared the relative ability of TGHQ, H(2)O(2), and EGF to activate EGFR and MAPKs and found that p38 MAPK activation is EGFR independent, whereas ERK1/2 activation occurs mainly through EGFR activation. TGHQ, H(2)O(2), and EGF induce different EGFR tyrosine phosphorylation profiles that likely influence the subsequent differential kinetics of MAPK activation. We next transfected LLC-PK(1) cells with a dominant negative p38 MAPK-expressing plasmid (pcDNA3-DNp38). TGHQ failed to induce phosphorylation of p38 MAPK and its substrate, MK-2, in pcDNA3-DNp38-transfected cells, indicating loss of function of p38 MAPK. In untransfected, pcDNA3 or pcDNA3-p38 (native)-transfected LLC-PK(1) cells, Hsp27 was intensively phosphorylated after TGHQ treatment, whereas in pcDNA3-DNp38-transfected cells, TGHQ failed to induce Hsp27 phosphorylation. Thus EGFR-independent p38 MAPK and EGFR-dependent ERK1/2 activation by TGHQ lead to the activation of two downstream signaling factors, i.e., histone H3 and Hsp27 phosphorylation, which have in common the potential ability to remodel chromatin.

Animals↗

PubMed2003

Afferent vagal pathways mediating respiratory reflexes evoked by ROS in the lungs of anesthetized rats.

We investigated the afferent vagal pathways mediating respiratory reflexes evoked by reactive oxygen species (ROS) in the lungs of anesthetized rats. Spontaneous inhalation of 0.2% aerosolized H(2)O(2) acutely evoked initial bradypnea followed by delayed tachypnea, which was frequently mixed with delayed augmented inspiration. The initial response was abolished after perivagal capsaicin treatment (PCT), but was prolonged during vagal cooling (VC) to 7 degrees C; PCT and VC are known to differentially block the conduction of unmyelinated C and myelinated fibers, respectively. The delayed responses were eliminated during VC but emerged earlier after PCT. Vagotomy, catalase (an antioxidant for H(2)O(2)), dimethylthiourea (an antioxidant for. OH), or deferoxamine (an antioxidant for. OH) largely or totally suppressed these reflexive responses, whereas sham nerve treatment, heat-inactivated catalase, saline vehicle, or iron-saturated deferoxamine failed to do so. These results suggest that 1) the H(2)O(2)-evoked initial and delayed airway reflexes are antagonistic and may result from stimulation of lung C fibers and rapidly adapting receptors, respectively, and 2) the reflex effects of H(2)O(2) are, in part, due to the action of. OH on these afferents.

Aerosols↗