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

Reversible spinal cord ischemia in rabbits induced a rapid loss of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) activity measured as incorporation of phosphate into exogenous substrates. About 70% of the activity was lost from the cytosolic fraction of spinal cord homogenates after 15 min of ischemia preceding irreversible paraplegia, which takes 25 min in this model. The loss of enzyme activity correlated with a loss of in situ renaturable autophosphorylation activity and a loss of CaM kinase II alpha and beta subunits in the cytosol detected by immunoblotting. CaM kinase II activity in the particulate fraction also decreased but the protein levels of the alpha and beta subunits increased. Thus ischemia resulted in an inactivation of CaM kinase II and a sequential or concurrent subcellular redistribution of the enzyme. However, denaturation and renaturation in situ of the CaM kinase subunits immobilized on membranes partly reversed the apparent inactivation of the enzyme in the particulate fraction. CaM kinase II activity was restored after reperfusion following short (< or = 25 min) durations of ischemia but not after longer durations (60 min) that result in irreversible paraplegia. The ischemia-induced inactivation of CaM kinase II, which phosphorylates proteins regulating many cellular processes, may be important in the cascade of events leading to delayed neuronal cell death.
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PMID:Inactivation and subcellular redistribution of Ca2+/calmodulin-dependent protein kinase II following spinal cord ischemia. 839 89

This article describes the pathophysiology of, and treatment strategy for, cerebral ischemia. It is useful to think of an ischemic lesion as a densely ischemic core surrounded by better perfused "penumbra" tissue that is silent electrically but remains viable. Reperfusion plays an important role in the pathophysiology of cerebral ischemia. Magnetic resonance imaging (MRI) and histological studies in rat focal ischemia models using transient middle cerebral artery (MCA) occlusion indicate that reperfusion after an ischemic episode of 2- to 3-hour duration does not result in reduction of the size of the infarct. Brief occlusion of the MCA produces a characteristic, cell-type specific injury in the striatum where medium-sized spinous projection neurons are selectively lost; this injury is accompanied by gliosis. Transient forebrain ischemia leads to delayed death of the CA1 neurons in the hippocampus. Immunohistochemical and biochemical investigations of Ca2+/calmodulin-dependent protein kinase II(CaM kinase II) and protein phosphatase (calcineurin) after transient forebrain ischemia demonstrated that the activity of CaM kinase II was decreased in the CA1 region of the hippocampus early (6-12 hours) after ischemia. However, calcineurin was preserved in the CA1 region until 1.5 days after the ischemic insult and then lost; a subsequent increase in the morphological degeneration of neurons was observed. We hypothesized that an imbalance of Ca2+/calmodulin dependent protein phosphorylation-dephosphorylation may be involved in delayed neuronal death after ischemia. In the treatment of acute ischemic stroke, immediate recanalization of the occluded artery, using systemic or local thrombolysis, is optimal for restoring the blood flow and rescuing the ischemic brain from complete infarction. However, the window of therapeutic effectiveness is very narrow. The development of effective neuroprotection methods and the establishment of reliable imaging modalities for an early and accurate diagnosis of the extent and degree of the ischemia are imperative.
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PMID:Pathophysiology and treatment of cerebral ischemia. 986 65

Brief ischemic episode, which in itself is not lethal, confers tolerance to subsequent ischemic insults. Since intracellular signal transduction system has been implicated in ischemic cell death, we studied the effect of pre-conditioning on the changes in the subcellular distribution of protein kinase Cgamma (PKCgamma) as well as CaM kinase II (CaMKII). Gerbils were pre-conditioned by a sublethal 2 min cerebral ischemia 24 h prior to lethal 5 min ischemia. The pre-conditioning generally downregulated PKCgamma and CaMKII in the CA1 hippocampus. Especially at the starting point of the second lethal ischemia, the cytosolic PKCgamma level was about 40% lower in the pre-conditioned group. Also, the crude synaptosomal CaMKII level at 24 h reperfusion following the second ischemia was significantly lower in the pre-conditioned group, showing enhanced recovery of CaMKII translocation. Present results suggest that ischemic pre-conditioning may downregulate calcium-mediated cell signaling system, enhancing normalization of calcium homeostasis, perturbed by the second ischemia of lethal duration.
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PMID:Ischemic pre-conditioning affects the subcellular distribution of protein kinase C and calcium/calmodulin-dependent protein kinase II in the gerbil hippocampal CA1 neurons. 1168 May 16

To clarify the involvement of intracellular signaling pathway and calpain in the brain injury and its protection by mild hypothermia, immunoblotting analyses were performed in the rat brain after global forebrain ischemia and reperfusion. After 30 min of ischemia followed by 60 min of reperfusion, Ca2+/calmodulin-dependent kinase II (CaM kinase II) and protein kinase C (PKC)-alpha, beta, gamma isoforms translocated to the synaptosomal fraction, while mild hypothermia (32 degrees C) inhibited the translocation. The hypothermia also inhibited fodrin proteolysis caused by ischemia-reperfusion, indicating the inhibition of calpain. These effects of hypothermia may explain the mechanism of the protection against brain ischemia-reperfusion injury through modulating synaptosomal function.
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PMID:Hypothermia inhibits translocation of CaM kinase II and PKC-alpha, beta, gamma isoforms and fodrin proteolysis in rat brain synaptosome during ischemia-reperfusion. 1189 78

To explore effects of Immunosuppressant FK506 on signal transduction pathway. we studied changes in subcellular distribution of protein kinase Cgamma (PKCgamma), CaM kinase II (CaMKII), as well as changes of tyrosine phosphorylation levels after ischemia. Male Mongolian gerbils were divided into 3 groups; FK506 (1 mg/kg, 3 mg/kg) and vehicle. FK506 was administered intravenously after 5 min ischemia. At the designated time points (0 time, 5 min ischemia, 1 hour, or 24 hour recovery), heads were frozen and samples were taken from CAI subfield of hippocampus. Western blot analysis was carried out with specific antibodies for PKCgamma, CaMKII, and phosphotyrosine. FK506 administration significantly decreased translocation of PKCgamma and CaMKII at 24 h of recovery (p < 0.05, ANOVA followed by Student-Newman Keuls' test) in P2 fraction. The levels of tyrosine phosphorylated p160, p140, p100, p90, and p80 in P2 fraction were also significantly decreased with FK506 treatment at 24 h of recovery. The persistently elevated PKCgamma and CaMKII level in P2 fraction which may be related to cell death, are attenuated with FK506 treatment. FK506 may contribute to recover calcium homeostasis in the post ischemic phase and promote cell survival.
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PMID:FK506 attenuates the post-ischemic perturbation of protein kinases and tyrosine phosphorylation in the gerbil hippocampal CA1 sectors. 1475 17


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