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Tarja Toimela

Bio: Tarja Toimela is an academic researcher from University of Tampere. The author has contributed to research in topics: Angiogenesis & Cell culture. The author has an hindex of 19, co-authored 42 publications receiving 881 citations. Previous affiliations of Tarja Toimela include National Institute of Chemical Physics and Biophysics.

Papers
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Journal ArticleDOI
TL;DR: The results support the idea that membrane ATPases are one target of the neurotoxic effect of pyrethroid compounds.

107 citations

Journal ArticleDOI
TL;DR: The study emphasized the toxicity of methylmercury to neural cells and showed that aluminum alters various cellular activities.
Abstract: Mercury and aluminum are considered to be neurotoxic metals, and they are often connected with the onset of neurodegenerative diseases. In this study, mercuric mercury, methylmercury and aluminum were studied in three different cell lines of neural origin. To evaluate the effects, mitochondrial cytotoxicity and apoptosis induced by the metals were measured after various incubation times. SH-SY5Y neuroblastoma, U 373MG glioblastoma, and RPE D407 retinal pigment epithelial cells were subcultured to appropriate cell culture plates and 0.01–1,000 µM concentrations of methylmercury, mercuric and aluminum chloride were added into the growth medium. In the assay measuring the mitochondrial dehydrogenase activity, WST-1, the cultures were exposed for 15 min, 24 or 48 h before measurement. Cells were allowed to recover from the exposure in part of the study. Apoptosis induced by the metals was measured after 6-, 24- and 48-h exposure times with the determination of activated caspase 3 enzyme. Mitochondrial assays showed a clear dose-response and exposure time-response to the metals. The most toxic was methylmercury (EC50 ~0.8 µM, 48 h), and the most sensitive cell line was the neuroblastoma cell line SH-SY5Y. Furthermore, there was marked mitochondrial activation, especially in connection with aluminum and methylmercury at low concentrations. This activation may be important during the initiation of cellular processes. All the metals tested induced apoptosis, but with a different time-course and cell-line specificity. In microscopic photographs, glioblastoma cells formed fibrillary tangles, and neuroblastoma cells settled along the fibrilles in cocultures of glial and neuronal cell lines during aluminum exposure. The study emphasized the toxicity of methylmercury to neural cells and showed that aluminum alters various cellular activities.

106 citations

Journal ArticleDOI
TL;DR: In conclusion, BBB models composed of RBE4 and ARPE-19 cells were able to distinguish between different toxicities, and AR PE- 19 cells are thus promising candidates for studies of drug penetration through the blood-brain barrier.

58 citations

Journal ArticleDOI
TL;DR: The results indicate that PBO is an effective synergist of pyrethrin and that it is very toxic in high concentrations, and confirm that neuronal sodium homeostasis is one target of the neurotoxic effect ofpyrethroid compounds.

53 citations

Journal ArticleDOI
TL;DR: The glutamate uptake was a sensitive target for the effects of tamoxifen and toremifene, and disturbances in this function could be considered as one of the possible mechanisms of retinal defects.
Abstract: The systemic drugs chloroquine and tamoxifen have caused retinal defects in human eye. The aim of our study was to investigate the effects of the amphiphilic drug tamoxifen, of its homologue toremifene, and of chloroquine on the glutamate uptake in retinal pigment epithelial (RPE) cells. Cultured human RPE cell line D407 and pig RPE cells were used in the study. Glutamate uptake was characterised and the glutamate transporters of pig RPE cells and the human RPE cell line D407 were compared to each other. The uptake of glutamate was studied using L-[3H]glutamate as a tracer. The radioactivity in the solubilised RPE was measured with a liquid scintillation counter. In the uptake experiments, the cells were exposed to the test drugs, to the selected glutamate receptor antagonists, and to the glutamate transporter inhibitors. Both RPE cell types exhibited a high-affinity transport system for glutamate. The glutamate transporter in RPE exhibited features characteristic of the uptake systems of neurotransmitters. The transport was Na+-dependent, and L- and D-aspartate were transported into the cell by the same transporter. Chloroquine had no effect on glutamate uptake, but tamoxifen and toremifene decreased the glutamate uptake of RPE cells dose-dependently both in pig RPE cells and in human RPE cell line. The IC50 values of tamoxifen and toremifene were lower for pig RPE cells, compared to the human RPE cell line D407. The glutamate uptake was a sensitive target for the effects of tamoxifen and toremifene, and disturbances in this function could be considered as one of the possible mechanisms of retinal defects.

46 citations


Cited by
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01 Jan 2004
TL;DR: Comprehensive and up-to-date, this book includes essential topics that either reflect practical significance or are of theoretical importance and describes numerous important application areas such as image based rendering and digital libraries.
Abstract: From the Publisher: The accessible presentation of this book gives both a general view of the entire computer vision enterprise and also offers sufficient detail to be able to build useful applications. Users learn techniques that have proven to be useful by first-hand experience and a wide range of mathematical methods. A CD-ROM with every copy of the text contains source code for programming practice, color images, and illustrative movies. Comprehensive and up-to-date, this book includes essential topics that either reflect practical significance or are of theoretical importance. Topics are discussed in substantial and increasing depth. Application surveys describe numerous important application areas such as image based rendering and digital libraries. Many important algorithms broken down and illustrated in pseudo code. Appropriate for use by engineers as a comprehensive reference to the computer vision enterprise.

3,627 citations

Journal ArticleDOI
TL;DR: Once MMP has been induced, it causes the release of catabolic hydrolases and activators of such enzymes (including those of caspases) from mitochondria, meaning that mitochondria coordinate the late stage of cellular demise.
Abstract: Irrespective of the morphological features of end-stage cell death (that may be apoptotic, necrotic, autophagic, or mitotic), mitochondrial membrane permeabilization (MMP) is frequently the decisive event that delimits the frontier between survival and death. Thus mitochondrial membranes constitute the battleground on which opposing signals combat to seal the cell's fate. Local players that determine the propensity to MMP include the pro- and antiapoptotic members of the Bcl-2 family, proteins from the mitochondrialpermeability transition pore complex, as well as a plethora of interacting partners including mitochondrial lipids. Intermediate metabolites, redox processes, sphingolipids, ion gradients, transcription factors, as well as kinases and phosphatases link lethal and vital signals emanating from distinct subcellular compartments to mitochondria. Thus mitochondria integrate a variety of proapoptotic signals. Once MMP has been induced, it causes the release of catabolic hydrolases and activators of such enzymes (including those of caspases) from mitochondria. These catabolic enzymes as well as the cessation of the bioenergetic and redox functions of mitochondria finally lead to cell death, meaning that mitochondria coordinate the late stage of cellular demise. Pathological cell death induced by ischemia/reperfusion, intoxication with xenobiotics, neurodegenerative diseases, or viral infection also relies on MMP as a critical event. The inhibition of MMP constitutes an important strategy for the pharmaceutical prevention of unwarranted cell death. Conversely, induction of MMP in tumor cells constitutes the goal of anticancer chemotherapy.

3,340 citations

Journal ArticleDOI
TL;DR: Mechanistic data give insights into the immunomodulatory potency of hydroxychloroquine and provide the rationale to search for more potent and/or selective inhibitors in antimalarial drugs.
Abstract: Despite widespread clinical use of antimalarial drugs such as hydroxychloroquine and chloroquine in the treatment of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and other inflammatory rheumatic diseases, insights into the mechanism of action of these drugs are still emerging. Hydroxychloroquine and chloroquine are weak bases and have a characteristic ‘deep’ volume of distribution and a half-life of around 50 days. These drugs interfere with lysosomal activity and autophagy, interact with membrane stability and alter signalling pathways and transcriptional activity, which can result in inhibition of cytokine production and modulation of certain co-stimulatory molecules. These modes of action, together with the drug’s chemical properties, might explain the clinical efficacy and well-known adverse effects (such as retinopathy) of these drugs. The unknown dose–response relationships of these drugs and the lack of definitions of the minimum dose needed for clinical efficacy and what doses are toxic pose challenges to clinical practice. Further challenges include patient non-adherence and possible context-dependent variations in blood drug levels. Available mechanistic data give insights into the immunomodulatory potency of hydroxychloroquine and provide the rationale to search for more potent and/or selective inhibitors. Hydroxychloroquine and chloroquine are antimalarial drugs commonly used for the treatment of rheumatic diseases. Multiple mechanisms might explain the efficacy and adverse effects of these drugs, but further investigation could lead to the development of more specific and potent drugs.

885 citations

Journal ArticleDOI
TL;DR: The article indicates that the hormetic dose response is the most fundamental dose response, significantly outcompeting other leading dose-response models in large-scale, head-to-head evaluations.
Abstract: This article provides a comprehensive review of hormesis, a dose-response concept that is characterized by a low-dose stimulation and a high-dose inhibition. The article traces the historical foundations of hormesis, its quantitative features and mechanistic foundations, and its risk assessment implications. The article indicates that the hormetic dose response is the most fundamental dose response, significantly outcompeting other leading dose-response models in large-scale, head-to-head evaluations. The hormetic dose response is highly generalizable, being independent of biological model, endpoint measured, chemical class, and interindividual variability. Hormesis also provides a framework for the study and assessment of chemical mixtures, incorporating the concept of additivity and synergism. Because the hormetic biphasic dose response represents a general pattern of biological responsiveness, it is expected that it will become progressively more significant within toxicological evaluation and risk assessment practices as well as have numerous biomedical applications.

588 citations