19 resultados para paramagnetic resonance


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Acc. Chem. Res., 2006, 39 (10), pp 788–796 DOI: 10.1021/ar050104k

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Background/Aims: Unconjugated bilirubin (UCB) impairs crucial aspects of cell function and induces apoptosis in primary cultured neurones. While mechanisms of cytotoxicity begin to unfold, mitochondria appear as potential primary targets. Methods: We used electron paramagnetic resonance spectroscopy analysis of isolated rat mitochondria to test the hypothesis that UCB physically interacts with mitochondria to induce structural membrane perturbation, leading to increased permeability, and subsequent release of apoptotic factors. Results: Our data demonstrate profound changes on mitochondrial membrane properties during incubation with UCB, including modified membrane lipid polarity and fluidity (P , 0:01), as well as disrupted protein mobility(P , 0:001). Consistent with increased permeability, cytochrome c was released from the intermembrane space(P , 0:01), perhaps uncoupling the respiratory chain and further increasing oxidative stress (P , 0:01). Both ursodeoxycholate, a mitochondrial-membrane stabilising agent, and cyclosporine A, an inhibitor of the permeability transition, almost completely abrogated UCB-induced perturbation. Conclusions: UCB directly interacts with mitochondria influencing membrane lipid and protein properties, redox status, and cytochrome c content. Thus, apoptosis induced by UCB may be mediated, at least in part, by physical perturbation of the mitochondrial membrane. These novel findings should ultimately prove useful to our evolving understanding of UCB cytotoxicity.

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Dissertação apresentada para obtenção do Grau de Doutor em Bioquímica, ramo de Bioquímica-Física, pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

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Dissertation presented to obtain the PhD degree in Biochemistry

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J Biol Inorg Chem (2011) 16:443–460 DOI 10.1007/s00775-010-0741-z

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J Biol Inorg Chem (2008) 13:1321–1333 DOI 10.1007/s00775-008-0416-1

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J Biol Inorg Chem. 2008 Jun;13(5):737-53. doi: 10.1007/s00775-008-0359-6

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J Biol Inorg Chem (2007) 12:777–787 DOI 10.1007/s00775-007-0229-7

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J Biol Inorg Chem (2007) 12:353–366 DOI 10.1007/s00775-006-0191-9

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J Biol Inorg Chem (2006) 11: 609–616 DOI 10.1007/s00775-006-0110-0

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Inorganica Chimica Acta 356 (2003) 215-221

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Dissertation submitted in Faculdade de Ciências e Tecnologia of Universidade Nova de Lisboa for the degree of Master in Biomedical Engineering

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Dissertation to Obtain the Degree of Master in Biomedical Engineering

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Based on the report for “Project IV” unit of the PhD programme on Technology Assessment (Doctoral Conference) at Universidade Nova de Lisboa (December 2011). This thesis research has the supervision of António Moniz (FCT-UNL and ITAS-KIT) and Michael Decker (Karlsruhe Institute of Technology-ITAS). Other members of the thesis committee are Carlos Alberto da Silva (University of Évora), José Maria de Albuquerque (Institute of Welding and Quality), Lotte Steuten (University of Twente), Mário Forjaz Secca (FCT-UNL) and Nelson Chibeles Martins (FCT-UNL).