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

In this study we examined the participation of cAMP formation in endothelin-1 (ET-1)-induced downregulation of ETB receptor mRNA in ROS 17/2 rat osteosarcoma cells. Dibutyryl cAMP induced downregulation of ETB receptor mRNA in a time-dependent manner. ET-1 induced production of inositol phosphates and an increase of cAMP level in ROS 17/2 cells. A stimulatory effect on cAMP level was also observed when A23187 plus PMA was added to the cells. The increase in cAMP level induced either by ET-1 or by A23187 plus PMA was inhibited by indomethacin. The downregulation of ETB receptor mRNA induced by ET-1 was significantly inhibited by indomethacin. These results suggest that the ET-1-induced downregulation of ETB receptor mRNA in ROS 17/2 cells may be partly mediated through the increase in cAMP level secondary to the activation of the phosphoinositide hydrolysis/Ca2+ transduction cascade.
J Cardiovasc Pharmacol 1995
PMID:Endothelin-1-induced downregulation of ETB receptor mRNA: participation of cAMP. 858 86

Reperfusion of the heart after a period of ischaemia leads to the opening of a nonspecific pore in the inner mitochondrial membrane, known as the mitochondrial permeability transition pore (MPTP). This transition causes mitochondria to become uncoupled and capable of hydrolysing rather than synthesising ATP. Unrestrained, this will lead to the loss of ionic homeostasis and ultimately necrotic cell death. The functional recovery of the Langendorff-perfused heart from ischaemia inversely correlates with the extent of pore opening, and inhibition of the MPTP provides protection against reperfusion injury. This may be mediated either by a direct interaction with the MPTP [e.g., by Cyclosporin A (CsA) and Sanglifehrin A (SfA)], or indirectly by decreasing calcium loading and reactive oxygen species (ROS; key inducers of pore opening) or lowering intracellular pH. Agents working in this way may include pyruvate, propofol, Na+/H+ antiporter inhibitors, and ischaemic preconditioning (IPC). Mitochondrial KATP channels have been implicated in preconditioning, but our own data suggest that the channel openers and blockers used in these studies work through alternative mechanisms. In addition to its role in necrosis, transient opening of the MPTP may occur and lead to the release of cytochrome c and other proapoptotic molecules that initiate the apoptotic cascade. However, only if subsequent MPTP closure occurs will ATP levels be maintained, ensuring that cell death continues down an apoptotic, rather than a necrotic, pathway.
Cardiovasc Res 2004 Feb 15
PMID:Mitochondrial permeability transition pore opening during myocardial reperfusion--a target for cardioprotection. 1496 70

In the present study, we tested the protective effect of 3,4,5,6-tetrahydroxyxanthone, a synthetic xanthone derivative, on myocardial ischemia-reperfusion injury in rats. Ischemia-reperfusion injury was induced by 30 min of global ischemia and 30 min of reperfusion in isolated rat hearts or 30 min coronary artery occlusion and 120 min reperfusion in vivo, respectively. Heart rate, coronary flow (CF), left ventricular pressure (LVP), and its first derivative (+/- dp/dt (max)) were recorded, and the activity of creatine kinase in coronary effluent and tumor necrosis factor-alpha (TNF-alpha) content in myocardial tissues were measured in vitro. The activity of serum creatine kinase, the level of TNF-alpha and interleukin-6 (IL-6), and myocardial infarct size were measured in vivo. 3,4,5,6-tetrahydroxyxanthone (30, 100 or 300 microM) caused a significant improvement of cardiac function (LVP and +/- dp/dt (max)) and a decrease in the release of creatine kinase in coronary effluent as well as the level of TNF-alpha in myocardial tissues in vitro. 3,4,5,6-tetrahydroxyxanthone (0.5 or 1.0 mg/kg, i.v.) also markedly decreased infarct size and the release of creatine kinase and TNF-alpha, and increased serum IL-6 level in vivo. These results suggest that 3,4,5,6-tetrahydroxyxanthone possesses a protective effect on myocardial ischemia-reperfusion injury, and that the protective effects of 3,4,5,6-tetrahydroxyxanthone may be related to inhibition of TNF-alpha production and stimulation of IL-6 generation by inhibition of ROS production.
Cardiovasc Drugs Ther 2004 Jul
PMID:3,4,5,6-Tetrahydroxyxanthone protects against myocardial ischemia-reperfusion injury in rats. 1536 25

The effect of Ginkgo biloba extract (EGb 761) was studied in rat hearts submitted to ischemia/reperfusion. Isolated hearts perfused in Langendorff mode were subjected to 60 minutes of global ischemia and 15 minutes of reperfusion. EGb 761 was administered by chronic or acute treatment: intra-peritoneal injections of 5 mg/Kg extract for 5 days, or 100 mg /L extract addition to the perfusion buffer, respectively. In hearts not treated with EGb 761, ischemia induced a 20% decrease in the concentration of membrane alpha-tocopherol. This effect was not worsened by reperfusion. alpha-tocopherol consumption was accompanied by about 650% increase in 6-ketoPGF1alpha release within 3 minutes of reperfusion. Moreover, ischemia induced activation of transcription factor NF-kappaB, as compared with the untreated group. In both chronic and acute treatment with EGb 761, heart concentration of alpha-tocopherol was completely spared during ischemia as much as after reperfusion, and a significant decrease of 6-ketoPGF1alpha release was observed at 3 minutes of reperfusion. Nuclear translocation of NF-kappaB was lowered during ischemia. EGb 761 might act as direct free radical scavenger or as tocopheryl radical recycler; in both cases sparing membrane vitamin E should affect phospholipase A2 activity. Finally, EGb 761, by lowering ROS produced during ischemia, challenges nuclear translocation of NF-kappaB.
J Cardiovasc Pharmacol 2004 Sep
PMID:The effect of Ginkgo biloba in isolated ischemic/reperfused rat heart: a link between vitamin E preservation and prostaglandin biosynthesis. 1547 34

In this brief essay we discuss the interrelationship between the cellular signaling effects induced by extracellular and intracellular ROS and nitric oxide in the context of doxorubicin (DOX) toxicity.
Cardiovasc Toxicol 2007
PMID:Iron signaling and oxidant damage. 1765 11

Growing evidence suggests that mechanisms which regulate the Ca2+ sensitivity of the contractile apparatus in vascular smooth muscle cells form the backbone of pressure-induced myogenic vasoconstriction. The modulation of Ca2+ sensitivity is suited to partially uncouple intracellular Ca2+ from constriction, thereby allowing the maintenance of tone with fully conserved function of other Ca2+-dependent processes. Following a brief review of 'classical' Ca2+-dependent signalling pathways involved in the myogenic response, the present review describes the emerging mechanisms that promote myogenic vasoconstriction via modulation of Ca2+ sensitivity. For the purpose of this review, Ca2+ sensitivity reflects the dynamic equilibrium between myosin light-chain kinase and myosin light-chain phosphatase activities in terms of its impact on vascular tone. Several signalling pathways (PKC, RhoA/Rho kinase, ROS) which have been identified as prominent regulators of Ca2+ sensitivity will be discussed. Although Ca2+ sensitivity modulation is clearly an important component of the myogenic response, attempts to integrate it into existing mechanistic models resulted in a two-phase model, with a predominant Ca2+-dependent 'initiation/trigger' phase followed by a Ca2+-independent 'maintenance' phase. We propose that the two-phase model is rather simplistic, because the literature reviewed here demonstrates that Ca2+-dependent and -independent mechanisms do not operate in isolation and are important at all stages of the response. The regulation of Ca2+ sensitivity, as an equal and complimentary partner of Ca2+-dependent processes, significantly enhances our understanding of the complex array of signalling pathways, which ultimately mediate the myogenic response.
Cardiovasc Res 2008 Jan
PMID:The emerging role of Ca2+ sensitivity regulation in promoting myogenic vasoconstriction. 1776 67

The decrease in the copy number of mitochondrial DNA (mtDNA) in cancer tissues might be associated with a decrease in oxidative mtDNA damage to achieve cancer immortalization and progression. Lung cancer specimens were collected from 29 patients with stage III non-small cell lung cancer (NSCLC) after neoadjuvant chemotherapy followed by surgical resection. The relative mtDNA copy number and the oxidative mtDNA damage (formation of 8-OHdG in mtDNA) of each cancer tissue were measured by quantitative real-time PCR. Seven female and 22 male lung cancer patients, with a mean age of 63.5 years were evaluated. Tumors of five patients became progressive, 13 stable, and 11 partially responsive after preoperative chemotherapy. Low mtDNA copy number (P=0.089) and low degree of oxidative mtDNA damage (P=0.036) were found to associate with tumor progression. Moreover, mtDNA copy number was significantly related to the degree of oxidative mtDNA damage (P=0.031). The mtDNA copy number and oxidative mtDNA damage were lower in advanced NSCLC after chemotherapy. This finding suggests that a decrease in the content of mtDNA may result in a decrease of mitochondrial density in cancer cells, which leads to a decrease of endogenous ROS production and reduction of ROS-triggered DNA damage to achieve immortalization.
Interact Cardiovasc Thorac Surg 2008 Dec
PMID:Low copy number and low oxidative damage of mitochondrial DNA are associated with tumor progression in lung cancer tissues after neoadjuvant chemotherapy. 1868 21

Vascular endothelium plays a crucial role in ensuring normal function and morphology of blood vessels, and many risk factors of atherosclerosis act via their effects on endothelial cells. However, endothelial dysfunction is induced by very different pathomechanisms. In principle, it is caused by an impaired bioavailability of nitric oxide (NO) due to an inhibited synthesis (eg, by asymmetric dimethylarginine [ADMA]) or increased consumption of formed NO (by reactive oxygen species [ROS]). ROS can be synthesized in the organism (eg, by different enzymes) or can be administered from the environment (eg, by cigarette smoking), whereas ADMA is the subject of endogenous metabolism only. Many studies have elucidated the system of pathomechanisms and targeted some as potential goals for therapeutic interventions. This review demonstrates roles of ROS, NO, ADMA, endothelin, and estrogen in endothelial function and dysfunction focusing on homocysteinemia and diabetes mellitus and provide examples for the medical treatment of endothelial dysfunction.
J Cardiovasc Pharmacol Ther 2008 Dec
PMID:Roles of oxidants, nitric oxide, and asymmetric dimethylarginine in endothelial function. 1894 74

In the past few years, a growing interest has been given to the possible antioxidant functions of a natural acid, synthesized in human tissues: alpha-lipoic acid (ALA). Both the oxidized (disulfide) and reduced (dithiol: dihydrolipoic acid, DHLA) forms of ALA show antioxidant properties. ALA administered in the diet accumulates in tissues, and a substantial part is converted to DHLA via a lipoamide dehydrogenase. Commercial ALA is usually a racemic mixture of the R and S forms. Chemical studies have indicated that ALA scavenges hydroxyl radicals, hypochlorous acid, and singlet oxygen. ALA exerts antioxidant effects in biological systems not only through direct ROS quenching but also via transition metal chelation. ALA has been shown to possess a number of beneficial effects both in the prevention and treatment of diabetes in experimental conditions. ALA presents beneficial effects in the management of symptomatic diabetic neuropathy and has been used in this context in Germany for more than 30 years. In cardiovascular disease, dietary supplementation with ALA has been successfully employed in a variety of in vivo models: ischemia-reperfusion, heart failure, and hypertension. More mechanistic and human in vivo studies are needed to determine whether optimizing the dietary intake of ALA can help to decrease cardiovascular diseases. A more complete understanding of cellular biochemical events that influence oxidative damage is required to guide future therapeutic advances.
J Cardiovasc Pharmacol 2009 Nov
PMID:Antioxidant properties of an endogenous thiol: Alpha-lipoic acid, useful in the prevention of cardiovascular diseases. 1999 23

Oxidative stress has been connected to various forms of cardiovascular diseases. Previously, we have been investigating the potential of new nitrogen-containing synthetic compounds using a neuronal cell model and different oxidative stress conditions in order to elucidate their potential to ameliorate neurodegenerative diseases. Here, we intended to extend these initial studies and investigate the protective role of four of those new synthetic compounds (FMA4, FMA7, FMA762 and FMA796) against oxidative damage induced to H9c2 cardiomyoblasts by tert-butylhydroperoxide (t-BHP). The data indicates that FMA762 and FMA796 decrease t-BHP-induced cell death, as measured by both sulforhodamine B assay and nuclear chromatin condensation evaluation, at non-toxic concentrations. In addition, the two mentioned compounds inhibit intracellular signalling mechanisms leading to apoptotic cell death, namely those mediated by mitochondria, which was confirmed by their ability to overcome t-BHP-induced morphological changes in the mitochondrial network, loss of mitochondrial membrane potential, increased expression of the pro-apoptotic proteins p53, Bax and AIF and activation of caspases-3 and -9. Importantly, our results indicate that the compounds' ROS scavenging ability plays a crucial role in the protection profile, as a significant decrease in t-BHP-induced oxidative stress occurred in their presence. Data obtained indicates that some of the test compounds may clearly prove valuable in a clinical context by diminishing cardiac injury associated to oxidative stress without any toxicity.
Cardiovasc Toxicol 2010 Mar
PMID:Nitrogen compounds prevent h9c2 myoblast oxidative stress-induced mitochondrial dysfunction and cell death. 2011 45


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