Environmental neurotoxin dieldrin induces apoptosis via caspase-3-dependent proteolytic activation of protein kinase C delta (PKCdelta): Implications for neurodegeneration in Parkinson's disease
| العنوان: | Environmental neurotoxin dieldrin induces apoptosis via caspase-3-dependent proteolytic activation of protein kinase C delta (PKCdelta): Implications for neurodegeneration in Parkinson's disease |
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| المؤلفون: | Vellareddy Anantharam, Yongjie Yang, Masashi Kitazawa, Anumantha G. Kanthasamy, Arthi Kanthasamy |
| المصدر: | Molecular Brain Kanthasamy, AG; Kitazawa, M; Yang, Y; Anantharam, V; & Kanthasamy, A. (2008). Environmental neurotoxin dieldrin induces apoptosis via caspase-3-dependent proteolytic activation of protein kinase C delta (PKCdelta): Implications for neurodegeneration in Parkinson's disease.. Molecular brain, 1, 12. doi: 10.1186/1756-6606-1-12. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/1h72v7w7Test Molecular Brain, Vol 1, Iss 1, p 12 (2008) |
| بيانات النشر: | Springer Science and Business Media LLC, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Male, Apoptosis, Mitochondrion, lcsh:RC346-429, Rats, Sprague-Dawley, chemistry.chemical_compound, 0302 clinical medicine, Neurotoxin, Dieldrin, 0303 health sciences, Caspase 3, Neurodegeneration, Dopaminergic, Brain, Cytochromes c, Parkinson Disease, Caspase Inhibitors, Mitochondria, 3. Good health, Cell biology, Protein Kinase C-delta, Biochemistry, Environmental Pollutants, Programmed cell death, Neurotoxins, DNA Fragmentation, Biology, 03 medical and health sciences, Cellular and Molecular Neuroscience, medicine, Animals, Molecular Biology, lcsh:Neurology. Diseases of the nervous system, 030304 developmental biology, Cell Nucleus, Research, medicine.disease, Rats, Enzyme Activation, nervous system, chemistry, Nerve Degeneration, Biocatalysis, Mutant Proteins, Reactive Oxygen Species, Protein Processing, Post-Translational, 030217 neurology & neurosurgery |
| الوصف: | Background In previous work, we investigated dieldrin cytotoxicity and signaling cell death mechanisms in dopaminergic PC12 cells. Dieldrin has been reported to be one of the environmental factors correlated with Parkinson's disease and may selectively destroy dopaminergic neurons. Methods Here we further investigated dieldrin toxicity in a dopaminergic neuronal cell model of Parkinson's disease, namely N27 cells, using biochemical, immunochemical, and flow cytometric analyses. Results In this study, dieldrin-treated N27 cells underwent a rapid and significant increase in reactive oxygen species followed by cytochrome c release into cytosol. The cytosolic cytochrome c activated caspase-dependent apoptotic pathway and the increased caspase-3 activity was observed following a 3 hr dieldrin exposure in a dose-dependent manner. Furthermore, dieldrin caused the caspase-dependent proteolytic cleavage of protein kinase C delta (PKCδ) into 41 kDa catalytic and 38 kDa regulatory subunits in N27 cells as well as in brain slices. PKCδ plays a critical role in executing the apoptotic process in dieldrin-treated dopaminergic neuronal cells because pretreatment with the PKCδ inhibitor rottlerin, or transfection and over-expression of catalytically inactive PKCδK376R, significantly attenuates dieldrin-induced DNA fragmentation and chromatin condensation. Conclusion Together, we conclude that caspase-3-dependent proteolytic activation of PKCδ is a critical event in dieldrin-induced apoptotic cell death in dopaminergic neuronal cells. |
| وصف الملف: | application/pdf |
| تدمد: | 1756-6606 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d7ab9405fc54860f17d48b22e7ef539eTest https://doi.org/10.1186/1756-6606-1-12Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d7ab9405fc54860f17d48b22e7ef539e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17566606 |
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