Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.22 (cdc2)
 8,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, the effects of melatonin on MPP+ -treated cerebellar granule neurons (CGNs) in culture were investigated. Results showed that MPP+ treatment significantly decreased cell viability and increased the apoptotic cell population at 24 and 48 hr. Calpain and caspase-3 activation was also determined, with results showing a strong increase in calpain (74%) and caspase 3 activity (70%), as measured by alpha-spectrin cleavage and fluorometric and colorimetric analysis, respectively. There are several studies suggesting that the activation of the cdk5/p35 pathway at its cleavage to cdk5/p25 may play a role in neuronal cell death in neurodegenerative diseases. Moreover, these studies indicate that this cleavage is mediated by calpains, and that MPP+ prompted an increase in cdk5 expression, as well as the cleavage of p35-p25, in a time-dependent manner. 1 mm Melatonin not only reduced the neurotoxic effects of MPP+ on cell viability, but also prevented apoptosis mediated by this Parkinsonian toxin in CGNs. 1 mm Melatonin reduced cdk5 expression, as well as the cleavage of p35-p25. These data indicate that melatonin possesses some neuro-protective properties against MPP+ -induced apoptosis. Moreover, these data suggest that the calpain/cdk5 signaling cascade has a potential role in the MPP+ -mediated apoptotic process in CGNs.
J Pineal Res 2006 Apr
PMID:Inhibition of the cdk5/p25 fragment formation may explain the antiapoptotic effects of melatonin in an experimental model of Parkinson's disease. 1649 62

Certain effects of melatonin on senescence were investigated. The experimental model used was 10-month-old senescence-accelerated mouse prone 8 (SAMP8). The mice in the experiment were administered melatonin (10 mg/kg) from the age of 1 month. Results showed that chronic administration of melatonin decreased cell loss in the cerebral cortex and reduced oxidative damage in protein and lipids. There are several studies suggesting that the activation of the cdk5/p35 pathway at its cleavage to cdk5/p25 may play a role in hyperphosphorylation of tau during aging and neurodegenerative diseases. Melatonin not only reduced the cerebral aging disturbances, but also prevented tau hyperphosphorylation present in the experimental model used in this study. Melatonin reduced cdk5 expression, as well as the cleavage of p35 to p25. The other tau kinase studied, GSK3beta, showed a reduction in this activity in comparison with SAMP8 nontreated SAMP8. These data indicate that melatonin possesses neuroprotective properties against cerebral damage gated to senescence. Moreover, these data suggest that the cdk5/GSKbeta signaling cascade has a potential role as a target for neurodegenerative diseases related to aging.
J Pineal Res 2007 Apr
PMID:Chronic administration of melatonin reduces cerebral injury biomarkers in SAMP8. 1743 56

A potential application of melatonin is its ability to rescue many cell types from cell death, because of its antioxidant properties. Likewise, recent studies suggest that melatonin may also be used as an anti-tumor drug, due to its anti-proliferative properties in tumor cells when administered at physiologic or pharmacologic doses. In the present study, we investigated the mechanisms involved in the apoptosis induced by acute exposure to melatonin and roscovitine in the rat dopaminergic neuroblastoma B65 cell line. Cell growth studies revealed that, at 24 hr of treatment, roscovitine blocked cell growth and induced apoptosis whereas melatonin delayed cell growth and induced a slight increase in the number of apoptotic nuclei. Melatonin also increased the percentage of cells in the G1-phase of the cell cycle, whereas roscovitine blocked cells in the G2/M-phase. Both compounds significantly downregulated the transcriptional activity of cdk4, while melatonin also downregulated cdk2 and cyclin D1. Taken together, our data show that melatonin at millimolar concentrations inhibits dopaminergic B65 proliferation, induces cell apoptosis, and modulates cell cycle progression by inhibiting the transcriptional activity of cyclins and cdks related to the progression of the G1-phase.
J Pineal Res 2008 Aug
PMID:The antiproliferative activity of melatonin in B65 rat dopaminergic neuroblastoma cells is related to the downregulation of cell cycle-related genes. 1828 48

Melatonin is an indolamine that is synthesized in the pineal gland and shows a wide range of physiological functions. Although the anti-aging properties of melatonin have been reported in a senescence-accelerated mouse model, whether melatonin modulates cellular senescence has not been determined. In this study, we examined the effect of melatonin on anticancer drug-induced cellular premature senescence. We found that the doxorubicin (DOX)-induced senescence of A549 human lung cancer cells and IMR90 normal lung cells was substantially inhibited by cotreatment with melatonin in a dose-dependent manner. Mechanistically, the DOX-induced G2/M phase cell cycle arrest and the decrease in cyclinB and cdc2 expression were not affected by melatonin. However, the DOX-induced increase in intracellular levels of ROS, which is necessary for premature senescence, was completely abolished upon melatonin cotreatment. In addition, the reduction in mitochondrial membrane potential that occurs upon DOX treatment was inhibited by melatonin. An aberrant increase in mitochondrial respiration was also significantly suppressed by melatonin, indicating that melatonin ameliorates the mitochondrial dysfunction induced by DOX treatment. The treatment of A549 cells with luzindole, a potent inhibitor of melatonin receptors, failed to prevent the effects of melatonin treatment on mitochondrial functions and premature senescence in cells also treated with DOX; this suggests that melatonin suppresses DOX-induced senescence in a melatonin receptor-independent manner. Together, these results reveal that melatonin has an inhibitory effect of melatonin on premature senescence at the cellular level and that melatonin protects A549 cells from DOX-induced senescence. Thus, melatonin might have the therapeutic potential to prevent the side effects of anticancer drug therapy.
J Pineal Res 2012 Nov
PMID:Melatonin suppresses doxorubicin-induced premature senescence of A549 lung cancer cells by ameliorating mitochondrial dysfunction. 2253 85