|
|
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result sql = Neuroprotective effects of caffeine against complex I inhibition-induced apoptosis are mediated by inhibition of the Atm/p53/E2F-1 path in cerebellar granule neurons.
Neuroprotective effects of caffeine against complex I inhibition-induced apoptosis are mediated by inhibition of the Atm/p53/E2F-1 path in cerebellar granule neurons.char = T;code = 84
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result sql = The aim of the present study was to evaluate the neuroprotective effects of caffeine, an inhibitor of ataxia telangiectasia mutated (ATM) enzyme and an antagonist of adenosine receptors, in two models of apoptosis in cerebellar granule neurons (CGNs): the inhibition of mitochondrial complex I by the neurotoxin MPP(+) and serum and potassium deprivation. We used cerebellar granule neurons because of low glial contamination. Cell viability was measured by the MTT method, and apoptosis was evaluated by assessing DNA fragmentation with flow cytometry or quantification of nuclear condensation. Our data indicate that the neuroprotective effects of caffeine in the MPP+ model of apoptosis are mediated through activation of the ATM/p53 pathway. In addition, caffeine decreased the expression of cyclin D and the transcription factor E2F-1, a regulator of apoptosis in neurons. Caffeine-mediated neuroprotection was not mediated through blockade of adenosine receptors because DPCPX and CGS-15943, two antagonists of these receptors, failed to attenuate apoptosis produced by MPP+ treatment. In addition, caffeine did not exert neuroprotective effects after serum and potassium withdrawal, a p53-independent model of apoptosis. Taken together, our findings indicate that DNA damage/ATM activation is a key component of MPP+-induced apoptosis in CGNs through activation of p53 and reentry into the cell cycle, specifically expression of the transcription factor E2F-1.
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result sql = Neuroprotective effects of caffeine against complex I inhibition-induced apoptosis are mediated by inhibition of the Atm/p53/E2F-1 path in cerebellar granule neurons.
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result sql = The aim of the present study was to evaluate the neuroprotective effects of caffeine, an inhibitor of ataxia telangiectasia mutated (ATM) enzyme and an antagonist of adenosine receptors, in two models of apoptosis in cerebellar granule neurons (CGNs): the inhibition of mitochondrial complex I by the neurotoxin MPP(+) and serum and potassium deprivation. We used cerebellar granule neurons because of low glial contamination. Cell viability was measured by the MTT method, and apoptosis was evaluated by assessing DNA fragmentation with flow cytometry or quantification of nuclear condensation. Our data indicate that the neuroprotective effects of caffeine in the MPP+ model of apoptosis are mediated through activation of the ATM/p53 pathway. In addition, caffeine decreased the expression of cyclin D and the transcription factor E2F-1, a regulator of apoptosis in neurons. Caffeine-mediated neuroprotection was not mediated through blockade of adenosine receptors because DPCPX and CGS-15943, two antagonists of these receptors, failed to attenuate apoptosis produced by MPP+ treatment. In addition, caffeine did not exert neuroprotective effects after serum and potassium withdrawal, a p53-independent model of apoptosis. Taken together, our findings indicate that DNA damage/ATM activation is a key component of MPP+-induced apoptosis in CGNs through activation of p53 and reentry into the cell cycle, specifically expression of the transcription factor E2F-1.
Publication: J. Neurosci. Res. 2007 Nov 1 ;85(14)::3079-88.
Publication Date: 2007 Nov 1
Study Author(s): Alvira, Daniel;Yeste-Velasco, Marc;Folch, Jaume;Casadesús, Gemma;Smith, Mark A;Pallàs, Mercè;Camins, Antoni;
Institution: Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona, Spain.
Shortcut link to this study:
Publication Date: 2007 Nov 1
Study Author(s): Alvira, Daniel;Yeste-Velasco, Marc;Folch, Jaume;Casadesús, Gemma;Smith, Mark A;Pallàs, Mercè;Camins, Antoni;
Institution: Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona, Spain.
Shortcut link to this study:
The aim of the present study was to evaluate the neuroprotective effects of caffeine, an inhibitor of ataxia telangiectasia mutated (ATM) enzyme and an antagonist of adenosine receptors, in two models of apoptosis in cerebellar granule neurons (CGNs): the inhibition of mitochondrial complex I by the neurotoxin MPP(+) and serum and potassium deprivation. We used cerebellar granule neurons because of low glial contamination. Cell viability was measured by the MTT method, and apoptosis was evaluated by assessing DNA fragmentation with flow cytometry or quantification of nuclear condensation. Our data indicate that the neuroprotective effects of caffeine in the MPP+ model of apoptosis are mediated through activation of the ATM/p53 pathway. In addition, caffeine decreased the expression of cyclin D and the transcription factor E2F-1, a regulator of apoptosis in neurons. Caffeine-mediated neuroprotection was not mediated through blockade of adenosine receptors because DPCPX and CGS-15943, two antagonists of these receptors, failed to attenuate apoptosis produced by MPP+ treatment. In addition, caffeine did not exert neuroprotective effects after serum and potassium withdrawal, a p53-independent model of apoptosis. Taken together, our findings indicate that DNA damage/ATM activation is a key component of MPP+-induced apoptosis in CGNs through activation of p53 and reentry into the cell cycle, specifically expression of the transcription factor E2F-1.
PMID: 17638302
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