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)

Pretreatment by a sublethal insult is associated with induction of stress proteins and with protection from subsequent injury. Heat pretreatment protects the brain from subsequent ischemia, and is shown here to protect primary astrocyte cultures from subsequent oxygen-glucose deprivation. To determine whether the expression of a single stress protein, HSP-70, could account for much of this protection, we expressed HSP-70 or beta-galactosidase in astrocytes using retroviral vectors. Only 12% of astrocytes expressing HSP-70 died after 7 hours of oxygen-glucose deprivation compared to 65% of astrocytes expressing beta-galactosidase and 82% of normal astrocytes. Our data provide direct evidence that selective expression of HSP-70 enhances the survival of astrocytes challenged with heat or oxygen-glucose deprivation.
 ...
PMID:Over-expression of HSP-70 protects astrocytes from combined oxygen-glucose deprivation. 873 Jul 98

The purpose of this study was to evaluate the protective effect of a new endotoxin analogue, monophosphoryl lipid A (MLA) in a rabbit model of myocardial ischemia/reperfusion and to show if this protection was mediated via synthesis of 70 kDa heat shock protein (HSP 70). Three groups of New Zealand White rabbits underwent 30 min coronary occlusion, followed by 4 hours reperfusion. First group of rabbits (n = 6) were treated with 0.35 ml vehicle (40% propylene glycol, 10% ethanol in water). The second and third group of rabbits (n = 6-8) were treated with MLA (35 micrograms/kg, i.v.) 12 and 24 hours prior to ischemia and reperfusion. MLA treatment either 12 or 24 h prior to ischemia/reperfusion demonstrated significantly reduced infarct size (12.5 +/- 1.7 and 14.7 +/- 2.1% for 12 and 24 h) when compared with vehicle control (40.4 +/- 8.6%, mean +/- S.E.M, p < 0.05). No significant differences in the infarct size was observed between the 12 and 24 h MLA treated groups. The area at risk was not significantly different between the three groups. Baseline values of heart rate, systolic and diastolic blood pressure were not significantly different between the control and MLA treated groups. However, the systolic as well as diastolic blood pressure during reperfusion were significantly lower in rabbits treated with MLA. Western blot analysis of the protein extracts of the hearts (n = 2/group) demonstrated no increase in the expression of the inducible form of HSP 70 following treatment with MLA. We conclude that MLA has significant anti-infarct effect in rabbit which is not mediated by the cardioprotective protein HSP 70. The anti-infarct effect of this drug is superior to the reported protective effects of delayed ischemic or heat stress preconditioning. We hypothesize that the pharmacologic preconditioning afforded by MLA is accomplished via a unique pathway that bypasses the usual intracellular signaling pathways which lead to the myocardial protection with the expression of heat shock proteins.
 ...
PMID:Monophosphoryl lipid A induces pharmacologic 'preconditioning' in rabbit hearts without concomitant expression of 70-kDa heat shock protein. 881 12

To separately analyze the hypoxic component of hypoxic-ischemic encephalopathy, rats were prepared such that their paO2 was maintained at 20 mmHg while maintaining systemic arterial pressures. During the 20-min experiment, brain oxygen concentration and extracellular amino acid concentrations were monitored. At sacrifice, the brains were studied for morphologic evidence of injury by immunocytochemical staining for the non-constitutive stress protein HSP-72 or neuronal death by acid fuchsin staining. Oxygenated rats subjected to global ischemia were prepared for comparison. In these experiment, hypoxia resulted in no increase in extracellular glutamate concentration, and no morphologic injury was detected. Thus, hypoxia without ischemia is well tolerated by brain.
 ...
PMID:The effects in vivo of hypoxia on brain injury. 883 24

The hepatic response to injury is orchestrated by the expression of different gene groups (i.e., heat shock and acute phase). In the present study, the expression of heat shock and acute phase genes was analyzed in the context of a localized injury, regional hepatic ischemia-reperfusion. Left and median liver lobes were subjected to 1 h of ischemia, whereas blood flow was maintained to the remainder of the organ. After the period of ischemia, the organ was reperfused, and samples of the ischemic and nonischemic liver were obtained at different time points during reperfusion. Expression of the heat shock gene, HSP 72, was detected only in the ischemic liver, whereas expression of the acute phase gene, beta-fibrinogen, and the interleukin-6-inducible gene, metallothionein, was maximally induced in the nonischemic liver and attenuated in the ischemic liver. To determine how the heat shock and acute phase responses were reprioritized during stress, expression of beta-fibronogen and HSP 72 was induced simultaneously in the same animal by administration of endotoxin and total body hyperthermia, respectively. Administration of endotoxin did not impede the expression of HSP 72; however, heat shock attenuated, but did not eliminate, the endotoxin-induced expression of beta-fibronogen. These observations suggest that the heat shock and acute phase responses are not mutually exclusive.
 ...
PMID:Distinct expression of heat shock and acute phase genes during regional hepatic ischemia-reperfusion. 885 85

Sublethal heat shock has been shown to produce tolerance in cells and tissues subsequently exposed to heat or ischemia/ATP depletion. We tested whether heating LLC-PK1 cells for 2 h at 42 degrees C induced heat shock protein-70 (HSP-70) gene expression and conferred tolerance against subsequent cyclosporine A (CyA) toxicity. HSP-70 mRNA was increased immediately after heat shock, returning to baseline by 4 h. HSP-70 protein increased by 1 h after heat shock and declined thereafter, approaching baseline after 72 h. Cells heat shocked at 4 and 24 h prior to CyA exposure were significantly more viable than controls, at CyA concentrations near the median lethal dose (LD50). Cytoprotection declined with time after heat shock, concurrent with declining HSP-70 protein levels. Sublethal CyA exposure (50 micrograms/ml) for 24 h produced upregulation of HSP-70 mRNA and protein. Pretreatment with 50 micrograms/ml CyA for 24 h followed by exposure to a toxic concentration of CyA (200 micrograms/ml) produced significant cytoprotection compared with untreated controls. In conclusion, HSP-70 protein induction by sublethal heat shock or CyA exposure was associated with tolerance against subsequent lethal CyA exposure.
 ...
PMID:Sublethal heat shock and cyclosporine exposure produce tolerance against subsequent cyclosporine toxicity. 885 18

Preconditioning the heart with brief episodes of ischemia paradoxically increases its resistance to subsequent ischemic episodes, and markedly limits infarct size. Although preconditioning is now considered as the most powerful antiischemic intervention known, its beneficial effects are short-lived since they are lost if the reperfusion period after preconditioning is extended past 2-3 h. There is, however, some evidence of a delayed phase of protection, manifest 24 h after the initial preconditioning stimulus, associated with a decrease in infarct size, a prevention of postischemic contractile dysfunction (stunning) and a reduction in endothelial injury. The delayed beneficial effects of preconditioning resemble those induced by prior heat stress, and might be related to the expression of stress proteins (heat shock proteins or HSP). Evidence for a role of HSP derives from observations showing that brief ischemia is a potent stimulus for HSP expression. Moreover, transfection of isolated cells with HSP or overexpression of HSP in transgenic mice renders the myocytes more resistant to ischemia. Once produced, HSP are believed to facilitate protein synthesis, stabilize newly formed proteins and repair denatured ones. Alternatively, delayed preconditioning may be mediated by antioxidant enzymes such as superoxide dismutase or catalase, which are also upregulated by ischemia and this could lead to a lesser production of oxygen-derived free radicals during reperfusion. Indeed, in isolated myocytes, prevention of hypoxia-induced expression of superoxide dismutase (using an antisense oligonucleotide) abolished the delayed protective effect of preconditioning. Importantly, recent in vivo evidence suggests that the delayed protection may be mediated by adenosine, through activation of A1-receptors, and by stimulation of protein kinase C. Finally, although the exact mechanisms by which preconditioning induces delayed protection are still mostly unknown, the fact that the expression of protective proteins such as HSP can be induced by many other means than ischemia suggests that it is possible to pharmacologically stimulate this expression and thus possibly mimic the endogenous protective pathway. This could lead to the development of new pharmacological interventions which induce delayed myocardial protection in clinical situations such as angioplasty, coronary bypass surgery or even in patients at high risk of infarction.
 ...
PMID:Delayed protection of the ischemic heart--from pathophysiology to therapeutic applications. 890 43

Oxygen free radical (OFR)-mediated oxidative stress in myocardial cells following ischemia could damage unit membrane and macromolecules such as nucleic acids (DNA). It is being reported that under this condition these cells produce antioxidants and heat shock proteins (HSP 70). It is implied that this family of proteins could function as a "molecular chaperone" in the cell and hence has to be transported to various target sites. This process is comparable to the induction of oxygen free radicals in melanocytes and its response, melanin production following UV light exposure stress. Lamp-1, trp-1 and tyrosinase are melanosomal-associated stress relief proteins which are involved in the production of melanin in the subcellular organelle, melanosomes. UV exposure studies as well as gene transfection studies and antisense hybridization in human melanoma cells clearly indicated an increase and marked coordinated interaction of all these stress relief proteins in melanogenesis. These proteins are synthesized in the endoplasmic reticulum and have to undergo posttranslation modification, sorting and posting to their respective target sites. We simultaneously identified and characterized an ER resident protein, calnexin. It became the potential candidate for "chaperoning" these proteins following translation. Based on the computer analysis of HSP 70 cDNA, we postulate that similar to stress response proteins in melanogenesis, stress relief proteins in myocardial cells may also be modulated by the same ER resident protein, calnexin.
 ...
PMID:Stress relief protein modulation by calnexin. 890 96

Chronic hypoxia inhibits rat thyroid function in vivo. To determine possible mechanisms, we studied the effect of hypoxia on iodide uptake, the involvement of second messengers, and cell membrane permeability in rat thyroid FRTL-5 cells. Since sublethal heat stress protects tissues from ischemia, we also determined effects of heat stress. The initial rate of iodide uptake in untreated cells was between 12.98 and 15.28 pmol/micrograms DNA/min. Hypoxia (5% O2) increased the rate of uptake in a time-dependent manner. Heating cells at 45 degrees C for 15 min (heat shock) prior to exposure to hypoxia for 3 days inhibited the increase in the initial rate of I-uptake. Using fura-2, we found that the resting [Ca2+]i in suspended FRTL-5 cells was 65 +/- 7 nM (n = 16). [Ca2+]i was not increased in cells exposed to hypoxia for 1 day, while a 3-day exposure increased [Ca2+]i by 43 +/- 4% (p < 0.05); no additional increase occurred after 7 days of exposure. When cells were heated prior to hypoxia exposure for 3 days, the hypoxia-induced increase in [Ca2+]i did not occur. Similar observations were found with inositol trisphosphates (InsP3). Exposure of cells to hypoxia for 3 days increased InsP3 from 0.08 +/- 0.02 (n = 5) to 0.32 +/- 0.04% total cpm (n = 5, p < 0.05), but sublethal heating of cells prior to hypoxia exposure prevented the increase. Three-day hypoxia increased PKC activity in the membrane fraction (from 67 +/- 7 to 86 +/- 4% of total activity, p < 0.05), and heat shock inhibited these changes also. Immunoblots showed that hypoxia treatment alone and heat shock plus hypoxia resulted in the translocation of PKC-alpha, -delta, -epsilon, and -zeta isoforms, whereas heat shock alone translocated only PKC-beta I, -beta II, and -zeta. Cell membrane integrity was assayed by trypan blue exclusion. Hypoxia alone for 3 days did not affect membrane permeability, but only 49 +/- 3% of cells excluded trypan blue when a 3-day hypoxia exposure was followed by a 6 h reoxygenation. Heat shock prior to hypoxia and reoxygenation protected cell membrane function. Heat shock also induced heat shock protein 70 kDa (HSP-70) synthesis at the transcriptional level. Results suggest that heat shock protects FRTL-5 cells from hypoxic injury, perhaps by inhibiting the initial rate of iodide uptake and second messengers. It is likely that HSP-70 plays an essential role in the process of protection.
 ...
PMID:Heat shock inhibits the hypoxia-induced effects on iodide uptake and signal transduction and enhances cell survival in rat thyroid FRTL-5 cells. 893 75

Hyperthermia-induced cardioprotection during myocardial ischemia may involve increased activity of antioxidative enzymes. In this study we investigated the effects of 3-amino-1,2,4-triazole (3-AT), an irreversible catalase inhibitor, in heat-shocked (HS) rabbits subjected to ischemia-reperfusion injury. Rabbits underwent whole body hyperthermia at 42 degrees C for 15 min. Twenty-four hours later, rabbits were administered either saline vehicle or 3-AT (1 or 2 g/kg i.p.) 30 min before undergoing 30 min of regional coronary occlusion and 3 h reperfusion. Controls did not undergo whole body hyperthermia and were given either saline or 3-AT. Heart rate and left ventricular pressure were recorded continuously during these experiments. Infarct area (tetrazolium staining) was normalized to anatomic risk zone size (microsphere autoradiography). Expression of HSP 71 was verified using Western blot analysis; myocardial catalase activity was determined in tissue biopsies. Infarct size was significantly reduced in HS rabbits (25.1 +/- 2.8%, P = 0.2; means +/- SE) compared with controls (53.6 +/- 4.7%). Treatment with 1 g/kg 3-AT attenuated HS-mediated cardioprotection (36.9 +/- 4.9%, P = 0.063 vs. HS); protection was abolished with 2 g/kg 3-AT (48.9 +/- 6.6%). Myocardial catalase activities were higher in tissue biopsies from HS rabbits (47.0 +/- 4.5 U/mg protein, P < or = 0.02) compared with controls (33.4 +/- 1.9 U/mg protein); catalase activities were significantly reduced in rabbits treated with 3-AT. In conclusion, whole body hyperthermia increases expression levels of HSP 71; myocardial catalase activity is also significantly increased. Myocardial protection is HS rabbits subjected to ischemia-reperfusion injury was reversed with 3-AT. These data suggest that increased intracellular activities of catalase and possibly other antioxidant enzymes is an important mechanism for hyperthermia-mediated cellular protection.
 ...
PMID:Effect of 3-aminotriazole on hyperthermia-mediated cardioprotection in rabbits. 896 53

Hyperbaric oxygen (HBO; 100% oxygen at 2 atmospheres absolute) was administered for 1 h to male Mongolian gerbils either for a single session or every other day for five sessions. Two days after HBO pretreatment, the gerbils were subjected to 5 min of forebrain ischemia by occlusion of both common carotid arteries under anesthesia. Seven days after recirculation, neuronal density per 1-mm length of the CA1 sector in the hippocampus was significantly better preserved in the five-session HBO pretreatment group (n = 10: 175.7 (47.8/mm, 54.9% of normal) than in the ischemic control group (n = 10: 26.2 (11.6/mm, 8.0% of normal) and in the single-session HBO pretreatment group (n = 7: 37.3 (21.7/mm, 11.4% of normal). Immunohistochemical staining for the 72-kDa heat-shock protein (HSP-72) in the CA1 sector performed 2 days following pretreatment revealed that the five-session HBO pretreatment increased the amount of HSP-72 present compared with that in the ischemic control group and in the single HBO pretreatment group. These results suggest that tolerance against ischemic neuronal damage was induced by repeated HBO pretreatment, which is thought to occur through the induction of HSP-72 synthesis.
 ...
PMID:Repeated hyperbaric oxygen induces ischemic tolerance in gerbil hippocampus. 897 93


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