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Depletion of Kinesin 5B Affects Lysosomal Distribution and Stability and Induce...
Cardoso, Carla M. P.; Groth-Pedersen, Line; Høyer-Hansen, Maria; Kirkegaard, Thomas; Corcelle, Elizabeth; Andersen, Jens S.; Jäättelä, MarjaBackground: Enhanced lysosomal trafficking is associated with metastatic cancer. In an attempt to discover cancer relevant lysosomal motor proteins, we compared the lysosomal proteomes from parental MCF-7 breast cancer cells with those from highly invasive MCF-7 cells that express an active form of the ErbB2 (DN-ErbB2). Methodology/Principal Findings: Mass spectrometry analysis identified kinesin heavy chain pr...
Surfactants as microbicides and contraceptive agents: a systematic in vitro study
Vieira, Otilia V.; Hartmann, Diego O.; Cardoso, Carla M. P.; Oberdoerfer, Daniel; Baptista, Marta; Santos, Manuel A. S.; Almeida, LuisBackground: The urgent need for cheap and easy-to-use protection against both unwanted pregnancies and sexually transmitted diseases has stimulated considerable interest in the use of surfactants as microbicides, anti-viral, and contraceptive agents in recent years. In the present study we report a systematic in vitro evaluation of the microbicidal, anti- viral and contraceptive potential of cationic, anionic, ...
The temperature dependence and involvement of mitochondria permeability transit...
Rytter, Anna; Cardoso, Carla M. P.; Johansson, Petra; Cronberg, Tobias; Hansson, Magnus J.; Mattiasson, Gustav; Elmér, Eskil; Wieloch, TadeuszThe aggravating effect of hyperglycemia on ischemic brain injury can be mimicked in a model of in vitro ischemia (IVI) using murine hippocampal slice cultures. Using this model, we found that the damage in the CA1 region following IVI in the absence or presence of 40 mm glucose (hyperglycemia) is highly temperature dependent. Decreasing the temperature from 35 to 31°C during IVI prevented cell death, whereas in...
Protection of tamoxifen against oxidation of mitochondrial thiols and NAD(P)H u...
Cardoso, Carla M. P.; Almeida, Leonor M.; Custódio, José B. A.The effects of tamoxifen (TAM) were studied on the mitochondrial permeability transition (MPT) induced by the prooxidant tert-butyl hydroperoxide (t-BuOOH) or the thiol cross-linker phenylarsine oxide (PhAsO), in the presence of Ca2+, in order to clarify the mechanisms involved in the MPT inhibition by this drug. The combination of Ca2+ with t-BuOOH or PhAsO induces mitochondrial swelling and depolarization of ...
Comparison of the changes in adenine nucleotides of rat liver mitochondria indu...
Cardoso, Carla M. P.; Moreno, António J. M.; Almeida, Leonor M.; Custódio, José B. A.The antiestrogen tamoxifen (TAM) inhibits the growth of different estrogen receptor (ER)-negative cells. Recently, multiple effects of TAM on mitochondrial bioenergetic functions have been pointed to explain its ER-independent cell death mechanisms. We have shown that TAM and its major active metabolite 4-hydroxytamoxifen (OHTAM) induce depolarization of the mitochondrial membrane potential ([Delta][Psi]) and u...
4-Hydroxytamoxifen induces slight uncoupling of mitochondrial oxidative phospho...
Cardoso, Carla M. P.; Moreno, António J. M.; Almeida, Leonor M.; Custódio, José B. A.The use of tamoxifen (TAM) has been questioned on the chemotherapy and chemoprevention of breast cancer due to several estrogen receptor-independent cytotoxic effects. As an alternative, its more active metabolite 4-hydroxytamoxifen (OHTAM) has been proposed with presumed lower side effects. In this work, the potential OHTAM toxicity on rat liver mitochondrial bioenergetics in relation to the multiple deleterio...
4-Hydroxytamoxifen is a potent inhibitor of the mitochondrial permeability tran...
Cardoso, Carla M. P.; Almeida, Leonor M.; Custódio, José B. A.The effects of 4-hydroxytamoxifen (OHTAM), the major active metabolite of the antiestrogen tamoxifen used in the breast cancer therapy, were studied on the mitochondrial permeability transition (MPT) and bioenergetic functions of mitochondria to evaluate the mechanisms underlying the cell death and toxic effects. The MPT was induced in vitro by incubating rat liver mitochondria with 1 mM inorganic phosphate plu...
Thiol protecting agents and antioxidants inhibit the mitochondrial permeability...
Custódio, José B. A.; Cardoso, Carla M. P.; Almeida, Leonor M.Etoposide (VP-16) is known to promote cell apoptosis either in cancer or in normal cells as a side effect. This fact is preceded by the induction of several mitochondrial events, including increase in Bax/Bcl-2 ratio followed by cytochrome c release and consequent activation of caspase-9 and -3, reduction of ATP levels, depolarization of membrane potential ([Delta][Psi]) and rupture of the outer membrane. These...
Mechanisms of the Deleterious Effects of Tamoxifen on Mitochondrial Respiration...
Cardoso, Carla M. P.; Custódio, José B. A.; Almeida, Leonor M.; Moreno, António J. M.Tamoxifen (TAM), the widely prescribed drug in the prevention and therapy of breast cancer, is a well-known modulator of estrogen receptor (ER) that also inhibits the proliferation of different cell types that lack the ER. However, the ER-independent action mechanisms of TAM and its side effects have not been yet clarified. Mitochondria are essential in supporting the energy-dependent regulation of cell functio...
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