Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Optic nerve transection results in retinal ganglion cell (RGC) death in adult mammals, after the alteration of gene expression of RGCs. To elucidate the molecular mechanism by which axotomy induces RGC death, we isolated the molecules up-regulated after optic nerve transection. One of these, axotomy-related [corrected] gene (ARG)357, an 898-amino-acid [corrected] protein containing a complete serine-threonine kinase domain, was isolated from a subtraction library of the rat retina. The sequence showed that this gene was a rat homolog of human c-Jun N-terminal kinase (JNK) inhibitory kinase and so belonged to the germinal center kinase-VIII subfamily of Sterile20s protein kinase. We designated ARG357 as rat JNK inhibitory kinase (JIK). Rat JIK was expressed ubiquitously in various tissues and was highly expressed in the retina, with selective expression in RGCs. After axotomy, BimEL and Hrk, which are BH3-only proteins, and rat JIK were up-regulated in RGCs. Overexpression of rat JIK in neuronal cells up-regulated the expression of BimEL, but not that of Hrk. These results indicate that JIK may contribute to axotomy-induced RGC death by up-regulating the expression of BH3-only protein.
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PMID:JNK inhibitory kinase is up-regulated in retinal ganglion cells after axotomy and enhances BimEL expression level in neuronal cells. 1609 29

Cilostazol (CLZ), a selective inhibitor of cyclic nucleotide phosphodiesterase 3, has been shown to reduce neuronal cell death after a transient cerebral infarction. The mechanism for this reduction was suggested to be an elevation of intracellular cAMP or an inhibition of tumor necrosis factor alpha. Optic nerve injury leads to retinal ganglion cell (RGC) death possibly from a deprivation of neurotrophic factors and/or the down-regulation of intracellular cAMP. The purpose of this study was to determine if CLZ can rescue RGCs after optic nerve transection by inhibiting cyclic nucleotide phosphodiesterase 3. To examine this, the mean densities of surviving RGCs after optic nerve transection were determined in retinas that received an intravitreal injection of CLZ and in retinas that received vehicle. Our results showed that the density of surviving RGCs in the retina with intravitreal CLZ were significantly higher than that with vehicle injection on day 7. The CLZ was effective in promoting the survival at more than 0.05% concentration. The neuroprotective effects induced by 0.05% CLZ could be observed even 14 days after optic nerve transection. Furthermore, combined application of protein kinase A (PKA) inhibitor, KT5720 (10 microM) and 0.05% CLZ significantly decreased the density of surviving RGCs compared to that with only 0.05% CLZ. Based on these data, we concluded that CLZ enhances the survival of axotomized RGC in vivo, possibly depending on the activation of PKA pathway.
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PMID:Cilostazol promotes survival of axotomized retinal ganglion cells in adult rats. 1839 44

Optic nerve head astrocytes become abnormal in eyes that have elevated intraocular pressure, and cultured astrocytes display altered protein expression after being subjected for > or = 1 days to elevated hydrostatic pressure. Here we show that 2-h elevated hydrostatic pressure (15 or 30 mmHg) causes phosphorylation of ERK1/2, ribosomal S6 protein kinase (p90(RSK)), and Na/H exchanger (NHE)1 in cultured rat optic nerve head astrocytes as judged by Western blot analysis. The MEK/ERK inhibitor U0126 abolished phosphorylation of NHE1 and p90(RSK) as well as ERK1/2. To examine NHE1 activity, cytoplasmic pH (pH(i)) was measured with BCECF and, in some experiments, cells were acidified by 5-min exposure to 20 mM ammonium chloride. Although baseline pH(i) was unaltered, the rate of pH(i) recovery from acidification was fourfold higher in pressure-treated astrocytes. In the presence of either U0126 or dimethylamiloride (DMA), an NHE inhibitor, hydrostatic pressure did not change the rate of pH(i) recovery. The findings are consistent with NHE1 activation due to phosphorylation of ERK1/2, p90(RSK), and NHE1 that occurs in response to hydrostatic pressure. These responses may precede long-term changes of protein expression known to occur in pressure-stressed astrocytes.
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PMID:Elevated hydrostatic pressure activates sodium/hydrogen exchanger-1 in rat optic nerve head astrocytes. 1941 99