Mitochondrial dysfunction and caspase activation in rat cortical neurons treated with cocaine or amphetamine
| العنوان: | Mitochondrial dysfunction and caspase activation in rat cortical neurons treated with cocaine or amphetamine |
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| المؤلفون: | Russell H. Swerdlow, A. Cristina Rego, Tice Macedo, Sandra M. Cardoso, Fernanda Borges, Catarina R. Oliveira, Teresa Cunha-Oliveira |
| المصدر: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | medicine.medical_specialty, Programmed cell death, Cell, Amphetamine-Related Disorders, Apoptosis, Pharmacology, Mitochondrion, Membrane Potentials, Cocaine-Related Disorders, Cocaine, Internal medicine, Cell Line, Tumor, medicine, Animals, Humans, Amphetamine, Molecular Biology, Caspase, Cerebral Cortex, Neurons, biology, General Neuroscience, Neurodegeneration, Cytochromes c, medicine.disease, Mitochondria, Rats, Disease Models, Animal, Endocrinology, medicine.anatomical_structure, Electron Transport Chain Complex Proteins, Caspases, Mitochondrial Membranes, Nerve Degeneration, biology.protein, Central Nervous System Stimulants, Neurology (clinical), Neuron, Energy Metabolism, Developmental Biology, medicine.drug |
| الوصف: | Drug abuse is associated with brain dysfunction and neurodegeneration, and various recreational drugs induce apoptotic cell death. This study examined the role of the mitochondrial apoptotic pathway in psychostimulant-induced neuronal dysfunction. Using primary neuronal cultures, we observed that amphetamine (IC50=1.40 mM) was more potent than cocaine (IC50=4.30 mM) in inducing cell toxicity. Apoptotic cell death was further evaluated using cocaine and amphetamine concentrations that moderately decreased cell reduction capacity but did not affect plasma membrane integrity. Compared to cocaine, amphetamine highly decreased the mitochondrial membrane potential, as determined using the fluorescent probe rhodamine-123, whereas both drugs decreased mitochondrial cytochrome c. In contrast to amphetamine, cocaine cytotoxicity was partly mediated through effects on the electron transport chain, since cocaine toxicity was ameliorated in mitochondrial DNA-depleted cells lacking mitochondrially encoded electron transport chain subunits. Cocaine and amphetamine induced activation of caspases-2, -3 and -9 but did not affect activity of caspases-6 or -8. In addition, amphetamine, but not cocaine, was associated with the appearance of evident nuclear apoptotic morphology. These events were not accompanied by differences in the release of the apoptosis-inducing factor (AIF) from mitochondria. Our results demonstrate that although both amphetamine and cocaine activate the mitochondrial apoptotic pathway in cortical neurons, amphetamine is more likely to promote apoptosis. |
| تدمد: | 0006-8993 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3c06c176d603012e702caed8d7f4bf76Test https://pubmed.ncbi.nlm.nih.gov/16638611Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3c06c176d603012e702caed8d7f4bf76 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00068993 |
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