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)

Cyclin-dependent kinase 5 (CDK5) is the 34 kDa catalytic subunit of a recently characterized neuronal cdc2-like protein kinase which appears to be involved in regulation of the neurocytoskeleton. Using the rat postdecapitative model, the effect of brain ischemia on histone H1 and tau protein CDK5 phosphorylating activity was examined. Histone H1 kinase activity increased in both cytosolic and particulate fractions of the hippocampus and neocortex after 5 min and 15 min of ischemia, then declined to control levels. CDK5 tau protein phosphorylating activity increased after 15 min ischemia; however, no electrophoretic shifts or changes in radiodensity of the tau bands were observed autoradiographically. On Western blot analysis, the CDK5 protein band did not change after 25 min ischemia, despite the increase and subsequent decline in enzyme activity. These data demonstrate a postischemic increase in CDK5 activity, an associated increase in CDK5 tau phosphorylating activity and a decline in activity in the absence of massive proteolysis. CDK5 appears to play a role in the events associated with neuronal response to ischemic injury.
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PMID:Cyclin-dependent protein kinase 5 activity increases in rat brain following ischemia. 930 12

Cyclin-dependent kinase 5 (CDK5) and ataxia-telangiectasia mutated (ATM) are involved in normal human neurodevelopment and serves as a switch between neuronal survival and death. However, the molecular mechanisms underlying CDK5-ATM-induced neuronal injury caused by intracerebral hemorrhage (ICH) remain unclear. In this work, we used rat ICH models and thrombin-induced cell models to investigate the potential role of CDK5-ATM signals. Our findings revealed that CDK5 protein levels and kinase activities (p-histone H1 expression) were enforced in hematoma-surrounding neuron tissues following ICH. Besides, the expression of p25, p-ATM, and active caspase-3 protein was also upregulated after ICH. According to in vitro assays, the expression of CDK5, p-ATM, and active caspase-3 was all upregulated in cell viability-decreasing ICH cell models. However, blocking of either CDK5 or ATM suppressed the phosphorylation of ATM and the expression of active caspase-3, and attenuated the inhibition of neuronal survival. When p35/p25 was silenced, CDK5-ATM pathway was further inhibited, and cell viability was obviously ameliorated. In conclusion, this work suggested that ATM could be phosphorylated by CDK5 to induce the active caspase-3 and neuronal injury when intracerebral hemorrhage or ischemia occurred. Thus, the CDK5-AMT signal pathway has an important role in ICH process and may be a therapeutic target to prevent brain injury.
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PMID:The Crucial Role of Cyclin-Dependent Kinase-5-Ataxia-Telangiectasia Mutated Axis in ICH-Induced Neuronal Injury of Rat Model. 2866 23