Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0599766 (functional recovery)
 13,441 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It was recently reported that in rats exposure to heat shock leads to appearance of a myocardial heat shock protein (HSP 70) and to an increase in myocardial catalase activity. This correlated with an improvement in post-ischemic function either in Langendorff-perfused hearts after low-flow ischemia or in working hearts after short-term, no-flow ischemia. We investigated the effect of the same hyperthermic treatment on functional recovery from no-flow ischemia of various durations in isolated working rat hearts performing at high or low external workloads. Rats were heated to core temperature of 42 degrees C for 15 min. No significant protein oxidation (% oxidized methionine) was observed 2.5 hr after treatment. A protein with migration characteristics similar to HSP 70 was observed in hearts of heat shocked rats 24 hr after this treatment while their myocardial catalase activity was not increased. Hearts of similarly treated rats were excised 24 hr after hyperthermia and perfused in a working mode with Krebs-Henseleit buffer (1.25 mM Ca2+, 11 mM glucose). At 15 cm H2O preload and 100 cm H2O afterload after 30 min no-flow ischemia, control hearts recovered to 36.9%, 2%, 47.6%, and 21.5% of the preischemic values of heart rate-peak systolic pressure product (RPP), aortic output, coronary flow, and cardiac output, respectively. After only 25 min of ischemia the respective recovered values were 61.6%, 11.5%, 58.7%, and 33.5%. Throughout the recovery period these hemodynamic values were consistently higher in hearts of heat shocked animals than in those of control hearts but the differences were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of catalase in myocardial protection against ischemia in heat shocked rats. 817 41

To explore the effects of heat stress (HS) in aged hypertrophied and nonhypertrophied rat hearts, postischemic recovery was investigated 15 mo after aortic constriction (AoB) or sham operation (Sham). Twenty-four hours after HS (42 degrees C; 15 min) or control treatment (normothermia), global ischemia was induced for 20 min in isolated AoB hearts and for 20 or 30 min in Sham hearts. After HS, postischemic recovery after 20-min ischemia in AoB hearts and 30-min ischemia in Sham hearts, respectively, was significantly better than in corresponding controls. In AoB hearts, cardiac output (CO), left ventricular developed pressure (LVDP), and the positive maximal first derivative of left ventricular pressure (+dP/dtmax) recovered to 33 +/- 26 (means +/- SD), 87 +/- 5, and 72 +/- 12%, respectively, after HS and to 5 +/- 8, 22 +/- 39, and 17 +/- 29% of preischemic values, respectively, in controls. Postischemic arrhythmias were significantly reduced in HS hypertrophied hearts, but creatine kinase (CK) loss was not reduced. In Sham hearts subjected to 30 min ischemia, CO, LVDP, and +dP/dtmax recovered to 20 +/- 20, 75 +/- 8, and 59 +/- 15%, respectively, after HS and to 3 +/- 8, 21 +/- 32, and 16 +/- 32% of preischemic values, respectively, in controls. Duration of arrhythmias and CK loss were not reduced in the heated hearts. When Sham hearts were subjected to only 20-min ischemia, functional recovery was not different in HS and control hearts, indicating that HS pretreatment extends the ischemic interval before irreversible injury occurs in the heart. In all HS Sham hearts, the myocardial 72-kDa HS protein (HSP 70) content was significantly increased. However, in HS AoB hearts, HSP 70 levels were not significantly different from the values in the control hearts. These results indicate that HS pretreatment induces cardioprotection in aged hypertrophied and nonhypertrophied rat hearts, which, however, cannot be unequivocally related to increased HSP 70 tissue contents.
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PMID:Heat stress protects aged hypertrophied and nonhypertrophied rat hearts against ischemic damage. 932 23

FK506 is a new FDA-approved immunosuppressant used for prevention of allograft rejection in, for example, liver and kidney transplantations. FK506 is inactive by itself and requires binding to an FK506 binding protein-12 (FKBP-12), or immunophilin, for activation. In this regard, FK506 is analogous to cyclosporin A, which must bind to its immunophilin (cyclophilin A) to display activity. This FK506-FKBP complex inhibits the activity of the serine/threonine protein phosphatase 2B (calcineurin), the basis for the immunosuppressant action of FK506. The discovery that immunophilins are also present in the nervous system introduces a new level of complexity in the regulation of neuronal function. Two important calcineurin targets in brain are the growth-associated protein GAP-43 and nitric oxide (NO) synthase (NOS). This review focuses on studies showing that systemic administration of FK506 dose-dependently speeds nerve regeneration and functional recovery in rats following a sciatic-nerve crush injury. The effect appears to result from an increased rate of axonal regeneration. The nerve regenerative property of this class of agents is separate from their immunosuppressant action because FK506-related compounds that bind to FKBP-12 but do not inhibit calcineurin are also able to increase nerve regeneration. Thus, FK506's ability to increase nerve regeneration arises via a calcineurin-independent mechanism (i.e., one not involving an increase in GAP-43 phosphorylation). Possible mechanisms of action are discussed in relation to known actions of FKBPs: the interaction of FKBP-12 with two Ca2+ release-channels (the ryanodine and inositol 1,4,5-triphosphate receptors) which is disrupted by FK506, thereby increasing Ca2+ flux; the type 1 receptor for the transforming growth factor-beta (TGF-beta 1), which stimulates nerve growth factor (NGF) synthesis by glial cells, and is a natural ligand for FKBP-12; and the immunophilin FKBP-52/FKBP-59, which has also been identified as a heat-shock protein (HSP-56) and is a component of the nontransformed glucocorticoid receptor. Taken together, studies of FK506 indicate broad functional roles for the immunophilins in the nervous system. Both calcineurin-dependent (e.g., neuroprotection via reduced NO formation) and calcineurin-independent mechanisms (i.e., nerve regeneration) need to be invoked to explain the many different neuronal effects of FK506. This suggests that multiple immunophilins mediate FK506's neuronal effects. Novel, nonimmunosuppressant ligands for FKBPs may represent important new drugs for the treatment of a variety of neurological disorders.
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PMID:FK506 and the role of immunophilins in nerve regeneration. 945 3

Heat stress (HS) and the subsequent expression of 72 kDa heat shock protein (HSP 72) has been shown to enhance post-ischemic functional recovery and reduce infarct size. Because the synthesis of heat shock proteins involves activation of heat shock transcription factors through phosphorylation, we hypothesized that inhibition of protein kinase C (PKC) would block HS mediated protection and expression of HSP 72 in the heart. Five groups of rats were studied (1) Sham anesthetized, (2) HS group--animals were heat shocked by raising the whole body core temperature to 42 degrees C for 15 min, (3) Vehicle group--HS rats treated with 50% DMSO in saline, (4) PKC inhibitor-treated group--specific PKC antagonist, chelerythrine chloride (5 mg/kg, i.p) given 30 min prior to HS and (5) Vehicle treated control--non-HS rats treated with vehicle prior to ischemia/reperfusion. Hearts were subjected to 30 min of regional ischemia and 90 min of reperfusion 24 h after HS. Risk area was delineated by injection of 10% Evan's blue and infarct size determined using computer morphometry of tetrazolium stained sections. Infarct size (% area at risk) reduced significantly from 49.4 +/- 2.3% (n = 7) in sham to 10.0 +/- 2.5% (p < 0.01) and 9.1 +/- 3.0% in HS and vehicle treated HS groups respectively (p < 0.05) Treatment with chelerythrine prior to HS increased infarct size to 49.4 +/- 2.3% (p < 0.05). Infarct size in chelerythrine-treated non-HS ischemic/reperfused heart was 40.7 +/- 5.4%, which did not differ significantly from vehicle-treated sham group. Western blot analysis demonstrated marked increase in HSP 72 in HS groups (with or without vehicle treatment) and pretreatment with chelerythrine chloride failed to inhibit the expression of HSP 72. The results suggest that HS-induced ischemic tolerance is mediated via PKC pathway and this protection does not appear to be directly related to the expression of HSP 72 in rat heart.
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PMID:Role of protein kinase C and 72 kDa heat shock protein in ischemic tolerance following heat stress in the rat heart. 1039 76

The findings of troponin I (TnI) proteolysis (in isolated rat hearts) and induction of selected sarcoplasmic reticulum (SR) calcium-regulatory genes (after repetitive total coronary occlusions in swine) have given rise to the hypothesis that the time course of functional recovery of stunned myocardium reflects the resynthesis of reversibly damaged proteins. Although stunning occurs after brief total occlusions and prolonged partial occlusions (ie, short-term hibernation), the time course of functional recovery varies from a few hours to several days, suggesting that the severity of protein damage or mechanisms responsible for the dysfunction may differ. To study this, we examined SR gene expression and TnI degradation in stunned myocardium produced by 10-minute total left anterior descending coronary artery (LAD) occlusions (n=4) or 1-hour partial LAD occlusions, in which flow was reduced to approximately 50% of control values for 60 minutes (n=6) in swine. One hour after reperfusion, LAD wall thickening was severely depressed in both models despite normal perfusion and no triphenyltetrazolium chloride evidence of necrosis. Normal myocardium exhibited TnI immunoreactivity at 31 kDa and a weak secondary band at 27 kDa. Irreversible injury or calpain activation in vitro produced a marked increase in the intensity of the 27-kDa band, consistent with TnI degradation. Stunned myocardium demonstrated no change in the 31- or the 27-kDa band, and the percentage of the 27- to 31-kDa band remained constant after 10-minute total occlusions (LAD, 5.9+/-0.9%; normal, 4.9+/-1.6%) and 1-hour partial occlusions (LAD, 8.5+/-1.9%; normal, 7.3+/-1.4%) and in sham controls (LAD, 10.9+/-1.5%; normal, 9.8+/-1.4%). Northern analysis showed no alterations in TnI or SR gene expression, but the stress protein HSP-70 was variably induced. Thus, stunned myocardium occurs without TnI degradation or altered SR gene expression, indicating that additional mechanisms are responsible for the reversible dysfunction after single episodes of regional ischemia in swine.
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PMID:Absence of troponin I degradation or altered sarcoplasmic reticulum uptake protein expression after reversible ischemia in swine. 1047 76

Potential long-term cardioprotection was investigated in an extensive experimental study. Lactobacillus cultivation components (LCC) were administered intravenously in anesthetized rats 1, 7, and 21 days before global ischemia (GI). GI was produced by full stop flow in isolated Langendorff-perfused hearts for 20 min and was followed by reperfusion. Control animals were injected with saline. LCC reduced reperfusion tachyarrhythmia significantly and improved functional recovery of the ischemized rat heart. These beneficial effects were associated with reduction of release of norepinephrine (NE) and prostacyclin at the first minute of reperfusion, activation of myocardial catalase, and overexpression of 70-kDa heat stress protein (HSP-70) at ischemia and reperfusion (P < 0.05). This cardioprotection was documented up to 21 days after a single injection of LCC. Thus Lactobacillus cultivation components are new nontoxic materials that produce marked long-term cardioprotection against ischemia-reperfusion damage. This effect is attributed to an activation of the cellular defense system, manifested by activation of the antioxidant pathway and by expression of protective proteins. NE is involved in this process, and the data also suggest a role for prostacyclin in this model of cardioprotection. The potential of LCC and related compounds working through similar mechanisms in the prevention and therapy of various ischemic heart syndromes should be explored.
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PMID:A new method of long-term preventive cardioprotection using Lactobacillus. 1077 53

Superoxide dismutase scavenges oxygen radicals, which have been implicated in ischemia/reperfusion (I/R) injury in the heart. Our experiments were designed to study the effect of a moderate increase of copper/zinc superoxide dismutase (CuZnSOD) on myocardial I/R injury in TgN(SOD1)3Cje transgenic mice. A species of 0.8 kb human CuZnSOD mRNA was expressed, and a 273% increase in CuZnSOD activity was detected in the hearts of transgenic mice with no changes in the activities of other antioxidant enzymes. Furthermore, immunoblot analysis revealed no changes in the levels of HSP-70 or HSP-25 levels. Immunocytochemical study indicated that there was increased labeling of CuZnSOD in the cytosolic fractions of both endothelial cells and smooth muscle cells, but not in the myocytes of the hearts from transgenic mice. When these hearts were perfused as Langendorff preparations for 45 min after 35 min of global ischemia, the functional recovery of the hearts, expressed as heart rate x LVDP, was 48 +/- 3% in the transgenic hearts as compared to 30 +/- 5% in the nontransgenic hearts (p <.05). The improved cardiac function was accompanied by a significant reduction in lactate dehydrogenase release from the transgenic hearts. Our results demonstrate that overexpression of CuZnSOD in coronary vascular cells renders the heart more resistant to I/R injury.
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PMID:Overexpression of CuZnSOD in coronary vascular cells attenuates myocardial ischemia/reperfusion injury. 1103 10

This study determined the role of body temperature during chronic exercise on myocardial stress proteins and antioxidant enzymes as well as functional recovery after an ischemic insult. Male Sprague-Dawley rats were exercised for 3, 6, or 9 wk in a 23 degrees C room (3WK, 6WK, and 9WK, respectively) or in a 4-8 degrees C environment with wetted fur (3WKC, 6WKC, and 9WKC, respectively). The colder room prevented elevations in core temperature. During weeks 3-9 the animals ran 5 days/wk up a 6% grade at 20 m/min for 60 min. Myocardial heat shock protein 70 (HSP 70) increased 12.3-fold (P < 0.05) in 9WK versus sedentary (SED) rats but was unchanged in the cold-room runners. Compared with SED rats, alphaB-crystallin was 90% higher in 9WKC animals, HSP 90 was 50% higher in 3WKC and 6WKC animals, and catalase was 23% higher in 3WK animals (P < 0.05 for all). Cytosolic superoxide dismutase increased and mitochondrial SOD decreased (P < 0.05) in 3WK and 6WK rats compared with 3WKC and 6WKC rats. Antioxidant enzymes returned to SED values in all runners by 9 wk. No differences were observed among any of the groups for glucose-regulated protein 75, heme oxygenase-1, or glutathione peroxidase. Mechanical recovery of isolated working hearts after 22.5 min of global ischemia was enhanced in 9WK (P < 0.05) but not in 9WKC rats. We conclude that exercise training results in dynamic changes in cardioprotective proteins over time which are influenced by core temperature. In addition, cardioprotection resulting from chronic exercise appears to be due to increased HSP 70.
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PMID:Effects of body temperature during exercise training on myocardial adaptations. 1129 31

Previously we have found that extracellular guanosine (Guo) has neuroprotective properties in in vitro and in vivo. Moreover, extracellular Guo significantly increased in the ipsilateral hemisphere within 2h following focal stroke in rats, and remained elevated for one week. Therefore, we hypothesized that Guo could be a potential candidate for a non-toxic neuroprotective agent. In the present study, we examined the effects of Guo on rats following permanent middle cerebral artery occlusion (MCAO). We also determined whether Guo can precondition neurons by modulating endoplasmic reticulum (ER) stress proteins. As most therapies employ a combination treatment regimen, we optimized the neuroprotection by combining pre- and post-MCAO treatments with Guo, attempting to reduce both ischemic cell death and improve functional recovery. A combination of 4mg/kg Guo given 30min pre-stroke and 8mg/kg Guo given 3, 24 and 48h post-stroke exerted the most significant decrease in infarct volume and sustainable improvement in neurological function. Moreover, these effects are not attributable to Guo metabolites. Measurements taken 6h post-MCAO from animals pre-treated with Guo did not reveal any significant changes in ER stress proteins (GRP 78 and 94) or HSP 70, but did reveal significantly increased levels of m-calpain. Thus, our data indicate that there is a treatment regimen for Guo as a neuroprotectant following ischemic stroke. The mechanism by which Guo confers neuroprotection may involve an increase in m-calpain, possibly resulting from a mild increase in intracellular calcium. M-calpain may be involved in the preconditioning response to ischemia by upregulating endogenous pro-survival mechanisms in neurons.
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PMID:Systemic administration of guanosine promotes functional and histological improvement following an ischemic stroke in rats. 2177 19

The heat shock protein 72 (HSP 72) is a universal marker of stress protein whose expression can be induced by physical exercise. Here we report that, in a localized model of spinal cord injury (SCI), exercised rats (given pre-SCI exercise) had significantly higher levels of neuronal and astroglial HSP 72, a lower functional deficit, fewer spinal cord contusions, and fewer apoptotic cells than did non-exercised rats. pSUPER plasmid expressing HSP 72 small interfering RNA (SiRNA-HSP 72) was injected into the injured spinal cords. In addition to reducing neuronal and astroglial HSP 72, the (SiRNA-HSP 72) significantly attenuated the beneficial effects of exercise preconditioning in reducing functional deficits as well as spinal cord contusion and apoptosis. Because exercise preconditioning induces increased neuronal and astroglial levels of HSP 72 in the gray matter of normal spinal cord tissue, exercise preconditioning promoted functional recovery in rats after SCI by upregulating neuronal and astroglial HSP 72 in the gray matter of the injured spinal cord. We reveal an important function of neuronal and astroglial HSP 72 in protecting neuronal and astroglial apoptosis in the injured spinal cord. We conclude that HSP 72-mediated exercise preconditioning is a promising strategy for facilitating functional recovery from SCI.
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PMID:Exercise preconditioning protects against spinal cord injury in rats by upregulating neuronal and astroglial heat shock protein 72. 2533 68


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