Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reduction in GluR2 subunit expression and subsequent increases in AMPA receptor mediated Ca(2+) currents were postulated to exacerbate glutamate neurotoxicity following seizures or global ischemia. To directly test the effects of shifting the GluR1/GluR2 subunit ratio on excitotoxicity, GluR2 antisense deoxyoligonucleotides (AS-ODNs) were applied to dissociated hippocampal cultures for 1-8 days. The GluR1/GluR2 protein ratio was examined immunohistochemically and by Western blotting. [Ca(2+)](i) concentrations were determined by ratiometric imaging of Fura 2-loaded cells. The cultures were exposed to glutamate, AMPA, NMDA or kainic acid (KA) 3 days after GluR2 knockdown and cell viability was determined 1 day later by MTT reduction assay or Trypan blue exclusion. Although GluR2 AS-ODNs increased the GluR1/GluR2 protein ratio in a time dependent manner, neurons and glia appeared healthy and MTT reduction values were similar to untreated and sense controls. Basal [Ca(2+)](i) levels were unchanged but [Ca(2+)](i) was selectively increased by agonist stimulation of AMPA receptors. Unexpectedly, delayed neurotoxicity was attenuated at saturating doses of glutamate while little difference in cell viability was observed at lower doses or with the other excitotoxins at any concentration. Therefore, there was a dissociation between rises in AMPA receptor-mediated Ca(2+) influx and neurotoxicity despite marked decreases in GluR2 but not GluR1 immunoreactivity. It is proposed that a modification of AMPA receptor stochiometry that raises agonist-stimulated Ca(2+) influx during an excitotoxic insult may have eventual neuroprotective effects.
 ...
PMID:GluR2 knockdown reveals a dissociation between [Ca2+]i surge and neurotoxicity. 1268 98

Celsior, a new preservation solution in thoracic organ transplantation was evaluated for efficacy in cold preservation of human hepatocytes and compared with University of Wisconsin solution (UW) and histidine-tryptophan-ketoglutarate solution (HTK, Custodiol). Human hepatocyte cultures were preserved at 4 degrees C in Celsior, UW and HTK for 2, 6, 12, 24 and 48 h with 6 h of reperfusion. Levels of lactate dehydrogenase (LDH; cell necrosis), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT; mitochondrial function), and adenosine 5'-triphosphate (ATP; loss of intracellular energy) were measured. Cell necrosis, mitochondrial dysfunction, and loss of ATP were significantly ( P<0.001, P<0.001, P<0.002, respectively) lower in Celsior than in HTK. The amount of cell necrosis and mitochondrial dysfunction in Celsior solution (CS) and UW was equal ( P=n.s.) up to 24 h and significantly lower in UW after 48 h ( P<0.001). Additionally, the intracellular level of ATP was significantly higher after ischemia ( P<0.001) and reperfusion from long-term ischemia (24, 48 h) ( P<0.002). We can conclude that Celsior was superior to HTK and equal to UW in the protection of human hepatocytes against cold preservation injury from ischemia and reperfusion. Furthermore, Celsior was effective in long-term preservation of human hepatocytes.
 ...
PMID:Celsior solution compared with University of Wisconsin solution (UW) and histidine-tryptophan-ketoglutarate solution (HTK) in the protection of human hepatocytes against ischemia-reperfusion injury. 1269 41

Perturbation of oxidant/antioxidant cellular balance, induced by cellular metabolism and by exogenous sources, causes deleterious effects to proteins, lipids, and nucleic acids, leading to a condition named "oxidative stress" that is involved in several diseases, such as cancer, ischemia-reperfusion injury, and neurodegenerative disorders. Among the exogenous agents, both H(2)O(2) and hyperthermia have been implicated in oxidative stress promotion linked with the activation of apoptotic or necrotic mechanisms of cell death. The goal of this work was to better understand the involvement of some stress-related proteins in adaptive responses mounted by human fibroblasts versus the oxidative stress differently induced by 42 degrees C hyperthermia or H(2)O(2.) The research was developed, switching off inducible nitric oxide synthase (iNOS) expression through antisense oligonucleotide transfection by studying the possible coregulation in the expression of HSP32 (also named HO-1), HSP70, and iNOS and their involvement in the induction of DNA damage. Several biochemical parameters, such as cell viability (MTT assay), cell membrane integrity (lactate dehydrogenase release), reactive oxygen species formation, glutathione levels, immunocytochemistry analysis of iNOS, HSP70, and HO-1 levels, genomic DNA fragmentation (HALO/COMET assay), and transmembrane mitochondrial potential (deltaPsi) were examined. Cells were collected immediately at the end of the stress-inducing treatment. The results, confirming the pleiotropic function of i-NOS, indicate that: (i). HO-1/HSP32, HSP70, and iNOS are finely tuned in their expression to contribute all together, in human fibroblasts, in ameliorating the resistance to oxidative stress damage; (ii). ROS exposure, at least in hyperthermia, in human fibroblasts contributes to growth arrest more than to apoptosis activation; and (iii). mitochondrial dysfunction, in presence of iNOS inhibition seems to be clearly involved in apoptotic cell death of human fibroblasts after H(2)O(2) treatment, but not after hyperthermia.
 ...
PMID:Adaptive responses to the stress induced by hyperthermia or hydrogen peroxide in human fibroblasts. 1270 75

Glutamate (1 mM), iodoacetate (0.01 mM) and ionomycin (0.25 micro M) are reported to induce several characteristics of ischemia and neuronal degeneration in vitro, e.g. glutamate and ionomycin lesion result in a disturbance of Ca(2+) homeostasis, iodoacetate impairment leads to an inhibition of energy metabolism, suppression of protein synthesis and generation of oxygen free radicals. In this study these three lesion models were used to investigate the effects of the nootropic drug Cerebrolysin (Cere) on the survival of cortical neurons in culture and on the occurrence of apoptosis. The viability of the cells was evaluated with the colorimetric MTT-reduction assay. Apoptosis was detected with Bisbenzimide (Hoechst:33258), a fluorescent DNA stain. Administration of Cere resulted in dose dependent neuroprotection independent from the kind of lesion. In the glutamate model the drug almost doubled neuronal viability compared to lesioned controls. After acute glutamate exposure Cere reduced the number of apoptotic cells significantly. In spite of the protective efficacy after cytotoxic hypoxia induced by iodoacetate, the drug significantly increased the number of apoptotic neurons, indicating a shift from necrosis to apoptosis. In contrast to previous studies investigating acute ionomycin lesions, the chronic Ca(2+)-overload used here did not increase the abundance of apoptosis compared to the unlesioned control. Summarizing the findings it can be suggested that Cere is able to stabilize Ca(2+) homeostasis, to protect protein synthesis and to counteract neuronal death in different in vitro medels of ischemia.
 ...
PMID:In vitro models of brain ischemia: the peptidergic drug cerebrolysin protects cultured chick cortical neurons from cell death. 1282 94

Diphenyl diselenide (PhSe)2 is an organic selenium compound that has been little studied. In this study we investigated the effects of (PhSe)2 (0.1-3 microM) in a classical model of in vitro brain ischemia, which consists of exposing rat hippocampal slices to oxygen-glucose deprivation (OGD). Hippocampal slices were exposed for 60 min to OGD and the cellular viability (performed by MTT assay) as well as the immunocontent of nitric oxide synthase inducible (iNOS) were evaluated after 180 min of a recovery period. OGD decreased cellular viability by 50% and increased more than twice the immunocontent of iNOS of hippocampal slices. (PhSe)2 (1 and 3 microM) added during OGD and the recovery period abolished both effects. These results demonstrate for the first time the neuroprotective effects of (PhSe)2. Although the selenium analog--ebselen--has been widely used in ischemia models, our results suggest that other selenoorganic compounds could be investigated as pharmacological tools against brain disorders.
 ...
PMID:Diphenyl diselenide protects rat hippocampal slices submitted to oxygen-glucose deprivation and diminishes inducible nitric oxide synthase immunocontent. 1296 45

Glucose-regulated proteins 75(grp75) is a member of hsp70 family. The expression of grp75 is upregulated during glucose starvation (such as ischemia). To evaluate grp75 function, CHL cells were cultured with glucose-free media for 20 h (A) and glucose-free media for 12 h + glucose-containing media for 8 h (ischemia reperfusion) (B). A constructed rat grp75 cDNA expression vector (pcDNA/grp75) was transfected into CHL cells and a cell strain that stably overexpressed grp75 was obtained. The transfected cells and untransfected cells(control group) were cultured with A or B. By MTT, LDH leakage measurement and flow cytometry analysis, growth rate of untransfected cells in B is significantly lower than that in glucose-containing media for 20 h (C) (p < 0.05) and A (p < 0.05). Growth rate of transfected cells is apparently higher than that of control group in B (p < 0.01). LDH liberation percentage of untransfected cells in B is obviously higher than that in C(p < 0.01) and it is not different from A(p > 0.05). LDH liberation percentage of transfected cells is apparently lower than that of control group in B(p < 0.01). Apoptosis of transfected cells is obviously lower by flow cytometry analysis. These results provide evidence for the cytoprotective function of grp75 during glucose starving and ischemia reperfusion.
 ...
PMID:[Molecular chaperone GRP75 reprove cells from injury caused by glucose deprivation]. 1472 51

Dopamine receptor agonists are protective in different models of neurodegeneration by both receptor-dependent and -independent mechanisms. We used SH-SY5Y cells, differentiated into neuron-like type, to evaluate if cabergoline, a dopamine D2 receptor agonist endowed with anti-oxidant activity, protects the cells against ischemia (oxygen-glucose deprivation model). Cabergoline protected the cells from ischemia-induced cell death in a concentration-dependent manner (EC(50)=1.2 microM), as demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release, and fluorescein diacetate-propidium iodide staining. This effect, observed even when the drug was added after oxygen-glucose deprivation, was not mediated by either dopamine D2 receptor activation or anti-apoptotic Bcl-2 protein over-expression (Western blotting analysis), but was linked to a reduction in cellular free radical loading (2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining) and membrane lipid peroxidation (thiobarbituric acid-reacting test). In conclusion, cabergoline protects in vitro neurons against ischemia-induced cell death, suggesting its possible use in the therapy of other neurodegenerative diseases in addition to Parkinson's disease.
 ...
PMID:Cabergoline protects SH-SY5Y neuronal cells in an in vitro model of ischemia. 1508 38

Mycophenolate mofetil (MMF) is a new immunosuppressive drug used to reduce acute rejection after heart transplantation. As with other immunosuppressive drugs, MMF therapy is associated with several adverse effects. However, the direct effects of MMF on myocardial tissue has not been yet evaluated. The aim of the work was thus to evaluate the effects of MMF on isolated cardiomyocytes (CM) in normal conditions and in an in vitro model of simulated ischemia (SI; substrate-free hypoxia) and reperfusion (R; reoxygenation). Myocyte-enriched cultures were prepared from newborn rat heart ventricles. The transmembrane potentials were recorded using conventional microelectrodes and the cell contractions were monitored with a photoelectric device. In basal conditions, MMF (10(-6) and 10(-5) M) exerted no significant effects on the survival and on the electrical and contractile activities of CM in culture, even during long-term exposure (up to 48 h). SI per se led to a gradual decrease and then an abortion of the spontaneous automaticity and electromechanical activity of CM. Pretreating CM with either 10(-6) or 10(-5) M MMF was able to reduce the SI-induced cell dysfunctions. The presence of MMF at these concentrations did not hamper the post-SI functional recovery of CM during reoxygenation. At 10(-5) M, MMF applied during reoxygenation only permitted a better recovery of CM. However, the mitochondrial function after reoxygenation, as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl-tetrazolium bromide (MTT) test, was not significantly influenced by the addition of MMF before as well as after ischemia. Conversely, MMF was able to reduce in this model the postischemic rise in xanthine and hypoxanthine. These data from CM-enriched model show that MMF: (i) had no cytotoxic effect, (ii) displayed a cytoprotective effect during SI, and (iii) exerted its beneficial effect at least partly through the decrease in the xanthine oxidase-dependent free radical production.
 ...
PMID:Physiological and metabolic actions of mycophenolate mofetil on cultured newborn rat cardiomyocytes in normoxia and in simulated ischemia. 1514 80

Production of reactive oxygen species (ROS) during islet purification by enzymatic digestion as well as during warm and cold ischemia causes islet cell damage. Recent reports have shown that activated Akt, the downstream protein after phosphatidylinositol (PI) 3-kinase, is involved in cell survival by phosphorylating several proteins that mediate apoptosis. We analyzed the role of PI3-kinase/Akt pathway activation using insulin or epidermal growth factor (EGF) on islet beta cell survival during oxidative stress. Canine islets and murine beta cell line (BTC) were cultured in the presence of hydrogen peroxide (H(2)O(2)) for 12 to 20 hours. Viability and cell death were measured by MTT assay. Maximum cell damage was observed with as little as 100 micromol/L of H(2)O(2). Pretreatment with 100 ng/mL of insulin significantly decreased cell damage. Meanwhile, the protective effect of insulin was partially blocked with an inhibitor of PI3-kinase, LY294002, suggesting the utilization of PI3-kinase/Akt signaling pathway for the observed cytoprotective effect. Similar to insulin, EGF also protected beta cells from oxidative stress. Our results suggest that PI3-kinase/Akt activation by insulin or EGF is beneficial for islet beta cell protection.
 ...
PMID:Epidermal growth factor and insulin inhibit cell death in pancreatic beta cells by activation of PI3-kinase/AKT signaling pathway under oxidative stress. 1519 3

The anti-atherogenic properties of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been well established in several circulatory beds. Increasing evidence suggests that statins may help attenuate ischemia-reperfusion injury, a beneficial effect that may be related to the antioxidant capabilities of statins; however, this remains controversial. We performed this study to determine whether the HMG-CoA reductase inhibitor cerivastatin can prevent oxidative stress-induced injury in cultured human aortic endothelial cells (HAEC). The HAEC were subjected to oxidative stress in the absence and presence of increasing concentrations of cerivastatin (50 nM-1,000 nM). Oxidative stress was induced by increasing concentrations of hydrogen peroxide or endogenous superoxide anions generated by the inhibition of superoxide dismutase using diethylthiocarbamate (10 mM). Cell viability and mitochondrial activity were measured by mitochondria-dependent 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) conversion. Cell morphology was also examined using light microscopy. Exposing HAEC to cerivastatin for 24 hours had no effect on cell viability using both cell morphology and MTT conversion: the HAEC incubated in 100 nM cerivastatin had 90% +/- 2.2% viability of the control. As expected, hydrogen peroxide produced a concentration-dependent decrease in cell viability. Varying concentrations of cerivastatin pretreatment for < or = 18 hours showed no protection of HAEC against hydrogen peroxide-induced injury. As a positive control, the prototype antioxidant N-acetyl-L-cysteine was cytoprotective even with the highest hydrogen peroxide concentration. Neither cerivastatin nor N-acetyl-L-cysteine protected HAEC against diethylthiocarbamate-induced oxidative injury at any concentration. In this study, cerivastatin did not protect cultured HAEC against oxidative stress induced by hydrogen peroxide or diethylthiocarbamate.
 ...
PMID:Cerivastatin does not prevent oxidative injury of human aortic endothelial cells. 1521 20


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