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Doxorubicin-Induced Cardiotoxicity: From Bioenergetic Failure and Cell Death to...

Carvalho, Filipa S.; Burgeiro, Ana; Garcia, Rita; Moreno, Antonio J.; Carvalho, Rui A.; Oliveira, Paulo J.

Doxorubicin (DOX) is an anticancer anthracycline that presents a dose-dependent and cumulative cardiotoxicity as one of the most serious side effects. Several hypotheses have been advanced to explain DOX cardiac side effects, which culminate in the development of life-threatening cardiomyopathy. One of the most studied mechanisms involves the activation of DOX molecule into a more reactive semiquinone by mitoch...


Inhibition of Mitochondrial Complex III Blocks Neuronal Differentiation and Mai...

Sandro, L. Pereira; Grãos, Mário; Rodrigues, Ana Sofia; Anjo, Sandra I.; Carvalho, Rui A.; Oliveira, Paulo J.; Arenas, Ernest; Ramalho-Santos, João

The mitochondrion is emerging as a key organelle in stem cell biology, acting as a regulator of stem cell pluripotency and differentiation. In this study we sought to understand the effect of mitochondrial complex III inhibition during neuronal differentiation of mouse embryonic stem cells. When exposed to antimycin A, a specific complex III inhibitor, embryonic stem cells failed to differentiate into dopaminer...


Rapeseed oil‑rich diet alters hepatic mitochondrial membrane lipid composition ...

Monteiro, João P.; Pereira, Cláudia V.; Silva, Ana M.; Maciel, Elisabete; Baldeiras, Inês; Peixoto, Francisco; Domingues, Maria R.; Jurado, Amália S.

Diet is directly related with physiological alterations occurring at a cell and subcellular level. However, the role of diet manipulation on mitochondrial physiology is still largely unexplored. Aiming at correlating diet with alterations of mitochondrial membrane composition and bioenergetics, Wistar-Han male rats were fed for 11, 22 and 33 days with a rapeseed oil-based diet and mitochondrial bioenergetics, a...


Mitochondrial membrane lipid remodeling in pathophysiology: A new target for di...

Monteiro, João P.; Oliveira, Paulo J.; Jurado, A. S.

Mitochondria are arbiters in the fragile balance between cell life and death. These organelles present an intricate membrane system, with a peculiar lipid composition and displaying transverse as well as lateral asymmetry. Some lipids are synthesized inside mitochondria, while others have to be imported or acquired in the form of precursors. Here, we review different processes, including external interventions ...


Dimethylaminopyridine derivatives of lupane triterpenoids cause mitochondrial d...

Bernardo, Telma C.; Cunha-Oliveira, Teresa; Serafim, Teresa L.; Holy, Jon; Krasutsky, Dmytro; Kolomitsyna, Oksana; Krasutsky, Pavel; Moreno, A. J. M.

Triterpenoids are a large class of naturally occurring compounds, and some potentially interesting as anticancer agents have been found to target mitochondria. The objective of the present work was to investigate the mechanisms of mitochondrial toxicity induced by novel dimethylaminopyridine (DMAP) derivatives of pentacyclic triterpenes, which were previously shown to inhibit the growth of melanoma cells in vit...


Dioxin-induced acute cardiac mitochondrial oxidative damage and increased activ...

Pereira, Susana P.; Pereira, Gonçalo C.; Pereira, Cláudia V.; Carvalho, Filipa S.; Cordeiro, Marília H.; Mota, Paula C.; Ramalho-Santos, J.

The environmental dioxin 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is classified as a Group 1 human carcinogen and teratogenic agent.We hypothesize that TCDD-induced oxidative stress may also interfere with mitochondrial ATP-sensitive potassium channels (mitoKATP), which are known to regulate and to be regulated by mitochondrial redox state. We investigated the effects of an acute treatment of male Wistar rats...


Mitochondrial disruption occurs downstream from β-adrenergic overactivation by ...

Branco, Ana F.; Sampaio, Susana F.; Wieckowski, Mariusz R.; Sardão, Vilma A.; Oliveira, Paulo J.

β-Adrenergic receptor stimulation plays an important role in cardiomyocyte stress responses, which may result in apoptosis and cardiovascular degeneration. We previously demonstrated that toxicity of the β-adrenergic agonist isoproterenol on H9c2 cardiomyoblasts depends on the stage of cell differentiation. We now investigate β-adrenergic receptor downstream signaling pathways and stress responses that explain ...


Nitrogen compounds prevent H9c2 myoblast oxidative stress-induced mitochondrial...

Silva, João P.; Sardão, V. A.; Coutinho, O. P.; Oliveira, Paulo J.

Oxidative stress has been connected to various forms of cardiovascular diseases. Previously, we have been investigating the potential of new nitrogen-containing synthetic compounds using a neuronal cell model and different oxidative stress conditions in order to elucidate their potential to ameliorate neurodegenerative diseases. Here, we intended to extend these initial studies and investigate the protective ro...


Mitochondrial bioenergetics of testicular cells from the domestic cat (Felis ca...

Mota, Paula; Amaral, Sandra; Martins, Luís; Pereira, Maria de Lourdes; Oliveira, Paulo J.; Ramalho-Santos, João

http://www.sciencedirect.com/science/article/B6TC0-4VKDMTB-2/2/353c03cb295c4b9b657bd182ae619622


Testicular mitochondrial alterations in untreated streptozotocin-induced diabet...

Amaral, Sandra; Mota, Paula C.; Lacerda, Beatriz; Alves, Marco; Pereira, Maria de Lourdes; Oliveira, Paulo J.; Ramalho-Santos, João

http://www.sciencedirect.com/science/article/B6W8G-4V3HFCC-2/2/73c61572e33e945983a6914b2dfbeb63


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    Financiadores do RCAAP

Fundação para a Ciência e a Tecnologia Universidade do Minho   Governo Português Ministério da Educação e Ciência Programa Operacional da Sociedade do Conhecimento União Europeia