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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied changes in myofibrillar function and protein profiles after complete global ischemia with anoxia in rat hearts. Hearts were exposed to global ischemia and anoxia (CGI) for 30 or 60 minutes at 37 degrees C, and myofibrils were prepared for measurement of Ca(2+)-dependent Mg(2+)-ATPase activity at pH 7.0 and 6.5. Hearts incubated in cold saline (1 +/- 1 degrees C) and nonincubated hearts served as controls. Maximum ATPase activity was unchanged at pH 7.0 and pH 6.5 in myofibrils from hearts treated with 30 or 60 minutes of CGI. At pH 7.0, the Hill coefficient, which is an index of cooperative interactions among thin-filament proteins, was unchanged after 30 minutes of CGI but was significantly increased after 60 minutes of CGI. A similar trend for increased cooperativity was observed when myofibrillar ATPase activity was measured at pH 6.5 in myofibrils from rat hearts made ischemic for 30 or 60 minutes. Both 30 and 60 minutes of CGI resulted in increased pCa50 values (half-maximally activating free [Ca2+]) at pH 7.0 and pH 6.5. Densitometric analysis of myofibrillar proteins separated with sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that troponin I and troponin T were degraded during 60 minutes of CGI. Two new protein bands appearing in ischemia-treated myofibrils were identified as partially degraded troponin I and troponin T with Western blots. The troponin I fragment could be phosphorylated by cAMP-dependent protein kinase. In addition, we observed phosphorylation of a protein band that corresponded to myosin light chain-2 in myofibrils from CGI-treated hearts. These results suggest that degradation of thin-filament proteins may contribute to the changes in cooperativity of Ca2+ regulation of ATPase activity observed in the myofibrils from rat hearts exposed to CGI.
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PMID:Alterations in myofibrillar function and protein profiles after complete global ischemia in rat hearts. 153 Nov 86

In order to investigate the role of Na+,K(+)-ATPase in the development of neuronal necrosis following cerebral ischemia, ischemia was induced in gerbils by occluding the common carotid artery unilaterally for 10 min. A time-course analysis revealed that significant reductions of the Na+,K(+)-ATPase activity in the cerebral cortex and hippocampus were manifested at 15 min, 30 min, and 1 h, and returned to the control level one day following recirculation. No apparent alterations of the Mg(2+)-ATPase activity, on the other hand, were obtained throughout the experimental period. Furthermore, Scatchard analyses of [3H]ouabain binding to the cerebral cortex membranes disclosed that the Bmax values invariably decreased without any change of Kd values following ischemia. It has also been shown that treatment of the animals with an agent known to mitigate ischemic neuronal necrosis, i.e. BY-1949, significantly reversed such derangements. These results suggest that the recovery of decreased Na+,K(+)-ATPase activity shortly after ischemia exerts a protective effect against ischemic brain damage.
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PMID:Neurochemical correlates of selective neuronal loss following cerebral ischemia: role of decreased Na+,K(+)-ATPase activity. 153 68

We have investigated hypertension-associated alterations in intracellular cations in the kidney by measuring intracellular pH, free Mg2+, free Ca2+, and Na+ concentrations in perfused normotensive and hypertensive rat (8-14 weeks old) kidneys using 31P, 19F, and double quantum-filtered (DQ) 23Na NMR. The effects of both anoxia and ischemia on the 23Na DQ signal confirmed its ability to detect changes in intracellular Na+. However, there was a sizable contribution of the extracellular Na+ to the 23Na DQ signal of the kidney. The intracellular free Ca2+ concentration, measured using 19F NMR and 5,5'difluoro-1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid, also increased dramatically during ischemia; the increase could be partly reversed by reperfusion. No significant differences were found between normotensive and hypertensive kidneys in the ATP level, intracellular pH, intracellular free Mg2+, and the 23Na DQ signal or in the extent of the extracellular contribution to the 23Na DQ signal. Oxygen consumption rates were also similar for the normotensive (5.02 +/- 0.46 mumol of O2/min/g) and hypertensive (5.47 +/- 0.42 mumol O2/min/g) rat kidneys. The absence of a significant difference in intracellular pH, Na+ concentration, and oxygen consumption between normotensive and hypertensive rat kidneys suggests that an alteration in the luminal Na+/H+ antiport activity in hypertension is unlikely. However, a highly significant increase (64%, p less than 0.01) in free Ca2+ concentration was found in perfused kidneys from hypertensive rats (557 +/- 48 nM, blood pressure = 199 +/- 5 mmHg, n = 6) compared with normotensive rats (339 +/- 21 nM, blood pressure = 134 +/- 6, n = 4) indicating altered renal calcium homeostasis in essential hypertension. An increase in intracellular free Ca2+ concentration without an accompanying change in the intracellular Na+ suggests, among many possibilities, that the Ca2+/Mg(2+)-ATPase may be inhibited in the hypertensive renal tissue.
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PMID:Multinuclear NMR studies of intracellular cations in perfused hypertensive rat kidney. 174 Apr 16

Intracellular free Mg2+ concentration [( Mg2+]i) has been shown to increase markedly during ischemia from 0.6 to 3.2 mM and remain elevated severalfold at 1.5 mM after reperfusion of the stunned heart. The significance of this rise in [Mg2+]i after reperfusion on cellular function is not well known. To determine whether this increase in free [Mg2+] would alter the function of the sarcoplasmic reticulum (SR), the effects of an increase in free [Mg2+] on the SR Ca(2+)-dependent Mg(2+)-adenosinetriphosphatase (ATPase) activity were examined in SR isolated from Langendorff-perfused, isovolumic rabbit hearts after 15 min of reversible ischemia (global stunning). Oxalate-supported Ca2+ transport, assessed under identical conditions (0.4 mM free Mg2+, 15 microM free Ca2+), was reduced from 495 +/- 29 to 395 +/- 27 nmol Ca2+.mg protein-1.min-1 in control and stunned hearts, respectively, indicating a defect in enzyme function. This defect was confirmed by a decrease in the maximal Ca(2+)-dependent Mg(2+)-ATPase activity. An increase in the free [Mg2+] to simulate conditions after reperfusion leads to a decrease in the Ca2+ sensitivity of the SR Mg(2+)-ATPase. Fifty percent activation was shifted from a control free [Ca2+] of 0.42 microM at 0.6 mM free [Mg2+] to 0.63 microM free [Ca2+] at 1.2 mM free [Mg2+], conditions that simulate the reperfused stunned myocardium. These results indicate that after stunning the observed decline in SR Ca2+ transport, determined under similar incubation conditions, may be further jeopardized by the sustained increase in free [Mg2+].(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of increased free [Mg2+]i with myocardial stunning on sarcoplasmic reticulum Ca(2+)-ATPase activity. 183 Apr 58

We induced cerebral complete ischemia (CCI) by "four-vessel" model. The changes of Na+,K(+)-ATPase, Ca2+, Mg(2+)-ATPase, phospholipase A2 (PLA2), total phospholipids on brain cellular membrane (BCM) at 30, 180, 360 min of reperfusion following 30 min CCI were observed. The effects of selective head cooling (SHC, 28C, surface cooling method), mannitol dehydration (MD), and selective head cooling-dehydration combined therapy (SHCDCT) on these changes were also investigated. Compared with non-ischemic, during reperfusion activities of Na+, K(+)-ATPase, Ca2+, Mg(2+)-ATPase decreased while PLA2 increased (P < 0.001), phospholipids decreased at 180 and 360 min of reperfusion (P < 0.01). SHC and SHCDCT blocked all above changes, MD had no effect. These results suggest that SHCDCT after starting reperfusion do promote recruitment of BCM function by blockade of the successive reperfusion damage on BCM.
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PMID:[Study of mechanism of selective head cooling-dehydration combined therapy for brain resuscitation: effect on function of brain cellular membrane]. 777 12

The rationale for these experiments is that administration of L-carnitine and/or short-chain acylcarnitines attenuates myocardial dysfunction 1) in hearts from diabetic animals (in which L-carnitine levels are decreased); 2) induced by ischemia-reperfusion in hearts from nondiabetic animals; and 3) in nondiabetic humans with ischemic heart disease. The objective of these studies was to investigate whether imbalances in carnitine metabolism play a role in the pathogenesis of diabetic peripheral neuropathy. The major findings in rats with streptozotocin-induced diabetes of 4-6 weeks duration were that 24-h urinary carnitine excretion was increased approximately twofold and L-carnitine levels were decreased in plasma (46%) and sciatic nerve endoneurium (31%). These changes in carnitine levels/excretion were associated with decreased caudal nerve conduction velocity (10-15%) and sciatic nerve changes in Na(+)-K(+)-ATPase activity (decreased 50%), Mg(2+)-ATPase (decreased 65%), 1,2-diacyl-sn-glycerol (DAG) (decreased 40%), vascular albumin permeation (increased 60%), and blood flow (increased 65%). Treatment with acetyl-L-carnitine normalized plasma and endoneurial L-carnitine levels and prevented all of these metabolic and functional changes except the increased blood flow, which was unaffected, and the reduction in DAG, which decreased another 40%. In conclusion, these observations 1) demonstrate a link between imbalances in carnitine metabolism and several metabolic and functional abnormalities associated with diabetic polyneuropathy and 2) indicate that decreased sciatic nerve endoneurial ATPase activity (ouabain-sensitive and insensitive) in this model of diabetes is associated with decreased DAG.
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PMID:Neural dysfunction and metabolic imbalances in diabetic rats. Prevention by acetyl-L-carnitine. 795 1

To investigate the time-dependent effects of ischemia, as modified by muscle fiber type composition, on sarcoplasmic reticulum (SR) function, Ca(2+)-ATPase activity (total minus basal) was measured in homogenates prepared from samples obtained from rat soleus and extensor digitorum longus (EDL) muscle of ischemic and contralateral controls. Ischemia was induced by occlusion of blood flow to one hindlimb for periods of 1, 2, and 3 h (n = 10 per group). In EDL, maximal Ca(2+)-ATPase activity (expressed in mumol.g wet wt-1.min-1) was higher (P < 0.05) in ischemic than in control at 1 h (80 +/- 10 vs. 56.5 +/- 5.3) and increased progressively with ischemia at both 2 h (88 +/- 4.6 vs. 53.1 +/- 2.8) and 3 h (116 +/- 3.8 vs. 67.8 +/- 3.2). In contrast, in soleus, increases (P < 0.05) in Ca(2+)-ATPase activity with ischemia were observed at 2 h (19.2 +/- 0.86 vs. 14.0 +/- 0.56) and 3 h (19.9 +/- 1.4 vs. 12.4 +/- 0.62) but not at 1 h (10.7 +/- 1.5 vs. 10.0 +/- 0.83). In both EDL and soleus, basal Mg(2+)-ATPase was unchanged with ischemia. On the basis of these findings, it can be concluded that ischemia results in an increase in the maximal SR Ca(2+)-ATPase activity but that the time course of the change is dependent on the fiber type composition of the muscle.
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PMID:Ischemia-induced alterations in sarcoplasmic reticulum Ca(2+)-ATPase activity in rat soleus and EDL muscles. 899 96

Opioid and alpha-adrenergic receptor activation protect the heart from ischemic damage. One possible intracellular mechanism to explain this is that an improvement in ATP availability contributes to cardioprotection. We tested this hypothesis by correlating postischemic left ventricular developed pressure (LVDP) and myofibrillar Ca(2+)-dependent actomyosin Mg(2+)-ATPase from isolated rat hearts treated with the kappa-opioid receptor agonist U-50488H (1 microM) or the alpha-adrenergic receptor agonist phenylephrine (10 microM) + propranolol (3 microM). Preischemic treatment with U-50488H or phenylephrine + propranolol improved postischemic LVDP recovery by 25-30% over control hearts. Ca(2+)-dependent actomyosin Mg(2+)-ATPase was found to be 20% lower in both U-50488H- and phenylephrine + propranolol-treated hearts compared with control hearts. The kappa-opioid receptor antagonist nor-binaltorphimine (1 microM) abolished the effects of U-50488H on postischemic LVDP and actomyosin Mg(2+)-ATPase activity. Reduced actomyosin ATP utilization was also suggested in single ventricular myocytes treated with either U-50488H or the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), because U-50488H and PMA lowered maximum velocity of unloaded shortening by 15-25% in myocytes. U-50488H and phenylephrine + propranolol treatment both resulted in increased phosphorylation of troponin I and C protein. These findings are consistent with the hypothesis that kappa-opioid and alpha-adrenergic receptors decrease actin-myosin cycling rate, leading to a conservation of ATP and cardioprotection during ischemia.
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PMID:Cardioprotection with kappa-opioid receptor stimulation is associated with a slowing of cross-bridge cycling. 1100 83

The review deals with the scientific activity of the Department of Biochemistry of Lipids of the Palladin Biochemistry Institute of the National Academy of Sciences of Ukraine. The estimation of the functional role of some major lipids and of the minor lipid components, namely, N-acylethanolamines (NAE), is the main problem of the scientific investigations of the Department. The role of some lipids in the pathogenesis of diseases accompanied by the oxidative stress was also studied. The Department was the first to find and identify NAE in neuroblastoma C1300 N18 cells. It was shown that NAE with long saturated acyl chains inhibited veratridine-activated fast sodium channels. NAE also activated uterine plasma membrane smooth muscle Ca2+, Mg(2+)-ATPase, and inhibited Fe(2+)-induced free radical oxidation in mitochondria. The results of these investigations served as a basis for development of pharmacological substances with membrane protective properties. It was shown that, at different diseases accompanied by the oxidative stress, a significant change in the lipid composition of cell membranes occurred. Sometimes these changes were adaptive in character, which favored the cell viability adaptation to pathological conditions. The new level of regulation of adaptive reactions can be accompanied by the development of additive injuries of cell viability, which may be caused by the altered level of biologically active cell lipid components. Based on the results of these investigations, the preparation intended for treatment of male infertility was developed. The pharmacological substances intended for treatment of morphine abuse and acute ischemia of myocardium were created.
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PMID:[Basic directions of research of the department of lipid biochemistry]. 1120 Apr 51

Calcium dobesilate possesses antioxidant properties and protects against capillary permeability by reactive oxygen species in the rat peritoneal cavity, but whether a similar action can take place in the diabetic rat retina is unknown. We investigated the oral treatment of diabetic rats with calcium dobesilate on the prevention of free radical-mediated retinal injury induced by ischemia/reperfusion (90 min ischemia followed by 3 min and/or 24 h of reperfusion). Streptozotocin-induced diabetic rats were orally treated with 50 and 100 mg/kg of calcium dobesilate for 10 days (n=12 in each group). In the first series of studies, calcium dobesilate was found to significantly reduce the maldistribution of ion content in diabetic ischemic/reperfused rat retina. Thus, in diabetic rats treated with 100 mg/kg/day calcium dobesilate, ischemia/reperfusion provoked: (i) 27.5% increase in retinal Na(+) content compared to 51.8% in the vehicle-treated group (P<0.05), and (ii) 59.6% increase in retinal Ca(2+) content compared to 107.1% in vehicle-treated animals (P<0.05). In the second series of studies, calcium dobesilate was found to significantly protect diabetic rat retina against inhibition of Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase activities by ischemia/reperfusion (54% and 41% reduction, respectively, with 100 mg/kg of calcium dobesilate) and also against changes in retinal ATP, reduced glutathione (GSH), and oxidized glutathione (GSSG) contents. In the third series of experiments, rats treated with 100 mg/kg of calcium dobesilate reduced the hydroxyl radical signal intensity to 41% (measured by electron paramagnetic resonance), induced by ischemia/reperfusion in diabetic rat retina. Finally, 100 mg/kg calcium dobesilate significantly reduced retinal edema (measured by the thickness of the inner plexiform layer) in diabetic rats. In conclusion, oral treatment with calcium dobesilate significantly protected diabetic rat retina against oxidative stress induced by ischemia/reperfusion. Whether the antioxidant properties of calcium dobesilate explain, at least in part, its beneficial therapeutic effects in diabetic retinopathy deserves further investigation.
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PMID:Antioxidant properties of calcium dobesilate in ischemic/reperfused diabetic rat retina. 1167 46


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