Made available in DSpace on 2015-08-20T17:10:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-03-03. Added 1 bitstream(s) on 2015-08-20T17:26:02Z : No. of bitstreams: 1 000843974.pdf: 2232932 bytes, checksum: d71102c081901322bd4ba52e2d8d373f (MD5) / O fipronil é um inseticida de amplo-espectro de ação utilizado extensivamente para o controle de pragas. Existem relatos descritos na literatura de intoxicação em animais e humanos provocada pelo composto, causando até a morte. Assim, torna-se bastante relevante elucidar os mecanismos de hepatotoxicidade do inseticida para o auxílio no tratamento em caso de intoxicação por parte dos mamíferos. O objetivo desse estudo foi caracterizar o mecanismo de toxicidade do fipronil em hepatócitos isolados de rato e o efeito da biotransformação sobre o seu potencial toxicológico. As concentração do fipronil utilizada foi de 5, 10, 15 e 25 μM em células permeabilizadas com digitonina e de 25, 50, 75 e 100 μM nas não permeabilizadas. A toxicidade do fipronil aos hepatócitos foi avaliada pelo consumo de oxigênio, potencial de membrana mitocondrial, concentração intracelular de ATP hepatócitos isolados de ratos normais ou previamente tratados com proadifen, homeostase intracelular do Ca 2+ e viabilidade celular. A viabilidade celular foi avaliada por meio da exclusão do azul de tripan em hepatócitos isolados de ratos normais e atividade das enzimas alanina transaminase (ALT) e aspartato transaminase (AST) em hepatócitos isolados de ratos normais ou previamente tratados com proadifen, um inibidor do citocromo P450. O fipronil reduziu a respiração mitocondrial em células energizadas com glutamato mais malato de maneira dose dependente, e diminuiu o potencial de membrana mitocondrial e esses efeitos foram acompanhados pela redução da concentração celular de ATP e pelo rompimento da homeostase intracelular do Ca 2+ . A viabilidade celular foi afetada pelo fipronil com maior potência nos hepatócitos isolados de ratos normais, indicando que os metabólitos do inseticida aumenta seu potencial toxicológico. Os resultados deste estudo indicam que a toxicidade do fipronil aos hepatócitos está... / Fipronil is an insecticide of broad-spectrum action used extensively for pest control. There are reports in the literature of animals and humans poisoning caused by the compound, ocacioning. Thus, it becomes quite important to elucidate the mechanisms of hepatotoxicity of the insecticide for treatment in case of intoxication by mammals. The aim of this study was to characterize the mechanism of toxicity of fipronil in isolated rat hepatocytes and the effect of biotransformation on its toxicological potential. The toxicity of fipronil was assessed by monitoring oxygen consumption and mitochondrial membrane potential, intracellular ATP concentration, Ca 2+ homeostasis and cell viability. The cell viability was evaluated by the tripan blue exclusion in hepatocytes isolated from normal rats and the activity of the enzyme alanine transaminase (ALT) and aspartate transaminase (AST) in hepatocytes isolated from normal rats or rats pretreated with proadifen, a cytochrome P450 inhibitor. Fipronil reduced mitochondrial respiration in cells energized with glutamate plus malate in a dose- dependent manner, and dissipated the mitochondrial membrane potential accompanied by reductions in ATP concentration and a disruption of intracellular Ca 2+ homeostasis. Cell viability was affected by fipronil with higher potency in hepatocytes isolated from normal rats, indicating that the metabolism of insecticide increases its toxicological potential. The results of this study indicate that the toxicity of fipronil to the hepatocytes is related to the inhibition of mitochondrial activity, leading to a decreased ATP synthesis and consequent alteration in intracellular Ca 2+ homeostasis, resulting in cell death

The Erv14 protein works as a cargo receptor in the COPII vesicles. Many proteins, including Na+, K+/H+ antiporter Nha1, which participates in the maintenance of cell alkali-metal-cation homeostasis, need Erv14 for their trafficking from the ER. When Erv14 is missing, the Nha1 antiporter is partially retained in the ER and its overall transport activity is affected. Although Erv14 interacts with the antiporter through Nha1's transmembrane domains, a shortened version of Nha1 lacking its long hydrophilic C-terminus does not require Erv14 for its efficient trafficking to plasma membrane. This thesis contributes to the understanding of the role of the Erv14 protein in the maintenance of alkali-metal-cation homeostasis in S. cerevisiae cells. Two S. cerevisiae strains lacking ERV14 gene were prepared and the effect of this deletion on the growth and salt tolerance of cells was studied. Using heterologous expression of NHA antiporters from various yeast species with variable lengths of their hydrophilic C-termini we studied localisation and function of these antiporters in S. cerevisiae cells in the presence and in the absence of Erv14 protein. Our results suggested that the length of the antiporter's C-terminus might play a role in its requirement of Erv14 presence for its trafficking through the...

Orientador: Fábio Erminio Mingatto / Banca: Flavia Thomas Verechia Pereira / Banca: Ana Angélica Henrique Fernandes / Resumo: O fipronil é um inseticida de amplo-espectro de ação utilizado extensivamente para o controle de pragas. Existem relatos descritos na literatura de intoxicação em animais e humanos provocada pelo composto, causando até a morte. Assim, torna-se bastante relevante elucidar os mecanismos de hepatotoxicidade do inseticida para o auxílio no tratamento em caso de intoxicação por parte dos mamíferos. O objetivo desse estudo foi caracterizar o mecanismo de toxicidade do fipronil em hepatócitos isolados de rato e o efeito da biotransformação sobre o seu potencial toxicológico. As concentração do fipronil utilizada foi de 5, 10, 15 e 25 μM em células permeabilizadas com digitonina e de 25, 50, 75 e 100 μM nas não permeabilizadas. A toxicidade do fipronil aos hepatócitos foi avaliada pelo consumo de oxigênio, potencial de membrana mitocondrial, concentração intracelular de ATP hepatócitos isolados de ratos normais ou previamente tratados com proadifen, homeostase intracelular do Ca 2+ e viabilidade celular. A viabilidade celular foi avaliada por meio da exclusão do azul de tripan em hepatócitos isolados de ratos normais e atividade das enzimas alanina transaminase (ALT) e aspartato transaminase (AST) em hepatócitos isolados de ratos normais ou previamente tratados com proadifen, um inibidor do citocromo P450. O fipronil reduziu a respiração mitocondrial em células energizadas com glutamato mais malato de maneira dose dependente, e diminuiu o potencial de membrana mitocondrial e esses efeitos foram acompanhados pela redução da concentração celular de ATP e pelo rompimento da homeostase intracelular do Ca 2+ . A viabilidade celular foi afetada pelo fipronil com maior potência nos hepatócitos isolados de ratos normais, indicando que os metabólitos do inseticida aumenta seu potencial toxicológico. Os resultados deste estudo indicam que a toxicidade do fipronil aos hepatócitos está... / Abstract: Fipronil is an insecticide of broad-spectrum action used extensively for pest control. There are reports in the literature of animals and humans poisoning caused by the compound, ocacioning. Thus, it becomes quite important to elucidate the mechanisms of hepatotoxicity of the insecticide for treatment in case of intoxication by mammals. The aim of this study was to characterize the mechanism of toxicity of fipronil in isolated rat hepatocytes and the effect of biotransformation on its toxicological potential. The toxicity of fipronil was assessed by monitoring oxygen consumption and mitochondrial membrane potential, intracellular ATP concentration, Ca 2+ homeostasis and cell viability. The cell viability was evaluated by the tripan blue exclusion in hepatocytes isolated from normal rats and the activity of the enzyme alanine transaminase (ALT) and aspartate transaminase (AST) in hepatocytes isolated from normal rats or rats pretreated with proadifen, a cytochrome P450 inhibitor. Fipronil reduced mitochondrial respiration in cells energized with glutamate plus malate in a dose- dependent manner, and dissipated the mitochondrial membrane potential accompanied by reductions in ATP concentration and a disruption of intracellular Ca 2+ homeostasis. Cell viability was affected by fipronil with higher potency in hepatocytes isolated from normal rats, indicating that the metabolism of insecticide increases its toxicological potential. The results of this study indicate that the toxicity of fipronil to the hepatocytes is related to the inhibition of mitochondrial activity, leading to a decreased ATP synthesis and consequent alteration in intracellular Ca 2+ homeostasis, resulting in cell death / Mestre

Grado de magíster en ciencias biológicas / La resistencia a la insulina (RI) es una condición metabólica frecuente, en la que hay una acción deficiente de esta hormona en los distintos tejidos en relación a un aumento de la glicemia. Es un factor de riesgo para el desarrollo de diabetes mellitus tipo 2 (DM2), dislipidemia, hipertensión arterial y otras enfermedades crónicas no transmisibles. La proteína C reactiva (PCR) es un marcador de inflamación sistémica observándose un aumento de baja magnitud en obesos, proporcional a la masa grasa corporal. La inflamación de bajo grado se ha relacionado con desarrollo de RI y DM2. Algunos estudios han demostrado asociación entre esta inflamación (medida por PCR) con RI, sin embargo, esta asociación no se ha analizado, a nivel poblacional, en población adulta joven Chilena. Hipótesis: La inflamación, determinada a través de PCR-us, se asocia con un aumento de la insulina y el HOMA, encontrándose también una gradiente de asociación directa, entre valores altos de PCR-us con insulina y HOMA elevados. Estas asociaciones serán más marcadas en mujeres. Objetivo: estimar la asociación de PCR con insulina y HOMA en adultos jóvenes. Metodología: Estudio de corte transversal de personas nacidas en la V Región, entre los años 1988 y 1992, entrevistadas entre 2014 y 2017 (n = 687) y que cuentan con las variables de interés: insulina, glicemia y PCR-us, además de antropometría, escolaridad, actividad física y tabaquismo. Se buscó la asociación de inflamación medida con PCR-us, con insulina y HOMA mediante regresiones lineales y logísticas. Resultados: Un 41% (IC: 37.3-45) de la población presenta HOMA elevado, 7% (IC: 5.1-8.9) insulina elevada y 38% (IC: 33-44) PCR-us elevada. Se encontró una asociación directa entre PCR-us con insulina (β: 0.3, IC: 0.09-0.5; p=0.005) y HOMA (β: 0.1, IC: 0.04-0.16; p=0.003). También entre inflamación (moderada) con insulina (β: 2.7, IC: 0.9-3.1; p=0.004) e inflamación (moderada y alta) con HOMA (β: 0.81 y 0.92, IC: 0.27-1.34 y 0.05-1.83; p=0.003 y 0.049 respectivamente) luego de ajustar por sexo, edad, escolaridad, tabaquismo, actividad física y obesidad. Conclusión: existe una asociación directa entre PCR con insulina y HOMA y entre PCR elevada con HOMA elevado.

Made available in DSpace on 2014-06-11T19:22:50Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-12-02Bitstream added on 2014-06-13T19:08:20Z : No. of bitstreams: 1 gomes_prl_me_prud.pdf: 496954 bytes, checksum: 1a8cc366f4f6c4e8b007f0dafc207ad0 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação para o Desenvolvimento da UNESP (FUNDUNESP) / A gravidez é um período de ajustes metabólicos e, quando associado ao tabagismo provoca alterações que trazem malefícios tanto à saúde materna quanto à saúde fetal. Assim, o estudo investigou o efeito da exposição à fumaça de cigarro sobre a expressão do transportador de glicose GLUT4 e parâmetros séricos e morfométricos de ratas prenhes e sua prole. Foram utilizadas ratas Wistar divididas em: CG- controle sacrificadas após a gestação, com prole adotada pelo grupo CL; CL - controle sacrificadas após o término da lactação; FG – expostas à fumaça de cigarro até o período gestacional e sacrificadas posteriormente, com prole adotada pelo grupo FL; FG – expostas à fumaça de cigarro até o fim da amamentação e posteriormente sacrificadas. As proles foram divididas por sexo e de acordo com a exposição ou não da rata à fumaça. Foram coletados sangue e tecidos para análise de glicemia e do conteúdo gênico e protéico de GLUT4. Nas ratas expostas à fumaça de cigarro, houve redução de peso corpóreo e de tecido adiposo, aumento da glicemia e modulação do transportador GLUT4 no músculo esquelético. Nas proles, houve... / Pregnancy is a period of metabolic adjustments, and when associated with cigarette smoke causes changes both to maternal health as the fetal. The study has investigated the effect of cigarette smoke exposure on the expression of glucose transporter GLUT4 and morphometric parameters and serum of pregnant smoker rats and their offspring. Wistar rats were divided in: CG- nonsmokers sacrificed after pregnancy with offspring adopted by CL; CL – nonsmoker group sacrificed after the end of lactation; FG – smoker group sacrificed after pregnancy with offspring adopted by FL; FL – smoker sacrificed after the end of lactation. The offspring was divided by sex and according to the protocol of their mothers. Blood and tissue were collected for analysis of glucose and the content of GLUT4 gene and protein. In smoker mothers, body weight and adipose tissue were reduced, glucose level was increased, and GLUT4 expression was higher in skeletal muscle. In offspring... (Complete abstract click electronic access below)

Submitted by Priscila Aparecida Faitanini Dandaro null (prisciladandaro@hotmail.com) on 2017-10-04T23:37:27Z No. of bitstreams: 1 DissertaçaCorrigidaPriscila1.pdf: 921624 bytes, checksum: 9e4fc1691299caf58ac61cace50e48ef (MD5) / Rejected by LUIZA DE MENEZES ROMANETTO (luizamenezes@reitoria.unesp.br), reason: Solicitado pela autora. on 2017-10-05T20:25:24Z (GMT) / Submitted by Priscila Aparecida Faitanini Dandaro null (prisciladandaro@hotmail.com) on 2017-10-06T11:22:23Z No. of bitstreams: 1 DissertaçaCorrigidaP.pdf: 920569 bytes, checksum: 9dafc763e4f119a842e7b097bc2ee074 (MD5) / Rejected by Luiz Galeffi (luizgaleffi@gmail.com), reason: Solicitamos que realize uma nova submissão seguindo as orientações abaixo: A ficha catalográfica deve ser inserida na página subsequente à folha de rosto. Por favor, corrija esta informação e realize uma nova submissão. Agradecemos a compreensão on 2017-10-11T13:21:16Z (GMT) / Submitted by Priscila Aparecida Faitanini Dandaro null (prisciladandaro@hotmail.com) on 2017-10-12T18:34:27Z No. of bitstreams: 1 submeter.pdf: 902917 bytes, checksum: 12f6af5239cf53974179e980e5ff6fe7 (MD5) / Approved for entry into archive by Monique Sasaki (sayumi_sasaki@hotmail.com) on 2017-10-18T16:44:11Z (GMT) No. of bitstreams: 1 dandaro_paf_me_bot.pdf: 902917 bytes, checksum: 12f6af5239cf53974179e980e5ff6fe7 (MD5) / Made available in DSpace on 2017-10-18T16:44:11Z (GMT). No. of bitstreams: 1 dandaro_paf_me_bot.pdf: 902917 bytes, checksum: 12f6af5239cf53974179e980e5ff6fe7 (MD5) Previous issue date: 2017-08-15 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / A utilização de preparados homeopáticos tem se tornado crescente na agricultura em especial nas plantas. Vários segmentos como a germinação, a produção de mudas, o controle de pragas e doenças de planta, o aumento de princípios ativos, desintoxicação de plantas por meios contaminantes e no metabolismo tem sido abordados através dos conceitos de Homeopatia. Os procedimentos que permitem reverter o quadro de estresse salino são pouco conhecidos, os custos são elevados e os recursos não são renováveis, tornando-se necessárias a adoção de novas tecnologias. O objetivo deste trabalho foi avaliar o efeito de preparados homeopáticos no desempenho agronômico e parâmetros fisiológicos em tomateiro-cereja submetido a estresse salino. O delineamento estatístico utilizado foi inteiramente casualizado, com oito tratamentos e cinco repetições. Foram avaliadas diferentes dinamizações de Natrum muriaticum (3CH; 5CH; 7CH; 9CH; 11CH; 13CH), e as testemunhas (água destilada e etanol 70%). As características avaliadas foram: altura (cm), diâmetro do colo (mm), número de folhas, número de flores por cacho, número de frutos, número de frutos por cachos, fluorescência da clorofila A, condutância estomática, teor relativo de água, potencial hídrico, determinação da área foliar, determinação de fitomassa fresca de frutos (gramas), teor de sólidos solúveis (°Brix) e teor de prolina do tomateiro-cereja. A aplicação da Ultradiluição de Natrum muriaticum promoveu incremento em todas as variáveis avaliadas referentes ao desempenho agronômico do tomateiro. Natrum muriaticum 11CH e 13CH atuam positivamente no desenvolvimento vegetativo e reprodutivo de tomate-cereja submetidos à estresse salino. / The use of homeopathic preparations has become increasing in agriculture, especially in plants. Several segments such as germination, production of seedlings, pest control and plant diseases, increased raw material assets, detoxification of plants by contaminating means and at metabolism had been reached by the concepts of Homeopathy. The procedures that allow the reversal of the salinity stresses are little known, the costs are high and the resources are not renewable, becoming necessary the adoption of new technologies. The objective of this work was to evaluate the effect of homeopathic preparations on agronomic performance and physiological parameters on cherry tomatoes submitted to saline stress. The statistical design was completely randomized, with eight treatments and five replicates. Different dynamizations of Natrum muriaticum (3CH; 5CH; 7CH; 9CH; 11CH; 13CH) and the controls (distilled water and 70% ethanol) were evaluated. The evaluated characteristics were: height (cm), lap diameter (mm), number of leaves, number of flowers per cluster, number of fruits, number of fruits per bunches, chlorophyll A fluorescence, stomatal conductance, relative water content, hydric potential, leaf area determination, fresh fruit phytomass determination (grams), soluble solids content (° Brix), and proline content of tomato-cherry. The application of the ultradilution of Natrum muriaticum promoted the increase in all evaluated variables related to the agronomic performance of the tomato. Natrum muriaticum 11CH and 13CH acts positively on vegetative and reproductive development of cherry tomatoes submitted to saline stress.

abstract: The coordination of group behavior in the social insects is representative of a broader phenomenon in nature, emergent biological complexity. In such systems, it is believed that large-scale patterns result from the interaction of relatively simple subunits. This dissertation involved the study of one such system: the social foraging of the ant Temnothorax rugatulus. Physically tiny with small population sizes, these cavity-dwelling ants provide a good model system to explore the mechanisms and ultimate origins of collective behavior in insect societies. My studies showed that colonies robustly exploit sugar water. Given a choice between feeders unequal in quality, colonies allocate more foragers to the better feeder. If the feeders change in quality, colonies are able to reallocate their foragers to the new location of the better feeder. These qualities of flexibility and allocation could be explained by the nature of positive feedback (tandem run recruitment) that these ants use. By observing foraging colonies with paint-marked ants, I was able to determine the `rules' that individuals follow: foragers recruit more and give up less when they find a better food source. By altering the nutritional condition of colonies, I found that these rules are flexible - attuned to the colony state. In starved colonies, individual ants are more likely to explore and recruit to food sources than in well-fed colonies. Similar to honeybees, Temmnothorax foragers appear to modulate their exploitation and recruitment behavior in response to environmental and social cues. Finally, I explored the influence of ecology (resource distribution) on the foraging success of colonies. Larger colonies showed increased consistency and a greater rate of harvest than smaller colonies, but this advantage was mediated by the distribution of resources. While patchy or rare food sources exaggerated the relative success of large colonies, regularly (or easily found) distributions leveled the playing field for smaller colonies. Social foraging in ant societies can best be understood when we view the colony as a single organism and the phenotype - group size, communication, and individual behavior - as integrated components of a homeostatic unit. / Dissertation/Thesis / Ph.D. Biology 2014

Recentemente, tem sido reconhecido que a água pode ser ao mesmo tempo uma fonte vital para os organismos e um veículo para eliminação de poluentes. Esse paradoxo pode ser considerado como parte da crise do presente ambiente que está inserida no conflito entre natureza e tecnologia, sendo acompanhado pelo emprego de biomarcadores, que consistem em indicadores bioquímicos e celulares da presença de contaminantes através da análise de fluidos corpóreos bem como células ou tecidos. O principal objetivo deste trabalho foi o de verificar quais os possíveis efeitos do cobre na homeostase do caranguejo de mangue Ucides cordatus expostos ao cobre na água (CuSO4) por diferentes períodos de tempo, através de teste agudo com exposição durante 24h e 96h e teste crônico com duração de 15 dias. Após a exposição dos animais à agua contaminada, estes foram crio-anestesiados pra dessensibilização e então foram retiradas alíquotas de hemolinfa e urina para determinação de concentrações de sódio, potássio, magnésio e cálcio, bem como as concentrações de glicose e lactato, além de brânquias e hepatopâncreas para a dosagem de enzimas como Na+/K+-ATPase, anidrase carbônica e a concentração da proteína metalotioneína, não esquecendo o músculo da quela que foi utilizado para determinação da concentração de glicogênio (assim como para o hepatopâncreas). Para complementar o amplo trabalho, foi determinado o transporte de cobre na membrana celular de brânquias e hepatopâncreas, através do qual foi possível verificar que a entrada do cobre pela membrana plasmática pode ocorrer através de diversas vias, podendo ser elas dependentes ou independentes de cálcio, porém é estritamente dependente da concentração de sódio no meio extra e intracelular, demonstrando interação entre transportadores para manutenção da homeostase. Além disso, o cobre se apresenta como um íon competidor com outros cátions como magnésio e potássio, além, claro, de alterar atividades enzimáticas como da Na+/K+-ATPase e anidrase carbônica. No entanto é válido notar que, principalmente para as brânquias anteriores, que são predominante respiratórias, houve aumento da síntese de metalotioneína, proteína esta induzida na presença de altas concentrações de cobre, que dentre outras funções, é principal componente da hemocianina, pigmento respiratório dos crustáceos / Recently, it has been recognized that water can be both a vital source for the organisms and a vehicle for disposal of pollutants. This paradox may be considered as part of the environment crisis that is inserted between nature and technology conflict, accompanied by the use of biomarkers that consists of cellular and biochemical indicators of contamination by analysis of body fluids as well as cells or tissues. The main objective of this study was to determine what the possible effects of copper homeostasis mangrove crab Ucides cordatus exposed to copper in water (CuSO4) for different periods of time, by testing acute exposure for 24h and 96h and chronic test, lasting 15 days. After exposure of the animals to contaminated water, they were cryo-anesthetized for desensitization and then aliquots of haemolymph and urine were collect to determine hemolymph and urine concentration of sodium, potassium, magnesium and calcium, and the concentrations of glucose and lactate as well as gills and hepatopancreas for measure enzymes such as Na+/K+-ATPase, carbonic anhydrase and metallothionein protein concentration, not forgetting the muscle which was used for the determination of glycogen concentration (as for the hepatopancreas). To complement the extensive study, it was determined copper transport in gills and hepatopancreas epithelial cells, whereby it was verified that the input of copper by plasma membrane can occur through various routes, which can be dependent or independent of calcium, but it is strictly dependent on the sodim concentration in intracellular and extracellular medium, showing interaction between transport proteins for maintaining homeostasis. Furthermore, copper is presented as a competitive with other cations such as magnesium and potassium, in addition of course to alter enzymatic activity as Na+/K+-ATPase and carbonic anhydrase. However it is worth noting that, especially prior to the anterior gill cells, which are predominant respiratory, that there was increased synthesis of metallothionein, which is a protein induced in the presence of high concentrations of copper, which among other functions, is the main component of hemocyanin, the respiratory pigment crustaceans

No description available.

Abstract In mammalian cells the pH gradient between the organelles, cytoplasm and extracellular space is strictly regulated. Maintenance of pH homeostasis is crucial for the normal function of the cell and its organelles. In solid tumours, cells often suffer from hypoxia, deprivation of nutrients and acidic extracellular milieu as a result of inadequate vascularisation. Cancer cells are also known to suffer from other pH abnormalities. Defective acidification of intracellular organelles as well as a reversed pH gradient across the plasma membrane have been detected in numerous tumour tissues and cells. Aberrant secretion of lysosomal hydrolases, loss of cell polarity and increased expression of tumour-specific proteins are common phenotypic changes of cancer cells. In this study, secretion of cathepsin D, a lysosomal aspartic hydrolase, was shown to result from the acidification defect of cancer cells. In normal cells cathepsin D is sorted in the Golgi complex by mannose-6-phosphate receptors and transported via endosomes to lysosomes. In breast and colorectal cancer cells having abnormally neutral endosomes receptors were shown to accumulate in endosomes resulting in the aberrant secretion of newly synthesised cathepsin D from the cells. Carcinoembryonic antigen (CEA) is an oncofetal protein widely used as a tumour follow-up marker. It is normally expressed at low levels and is localised at the apical surface of epithelial cells via a glycosyl phosphatidyl inositol (GPI) anchor. In cancer cells the expression of CEA is increased and the protein is found over the entire surface of cells. In this study, the tumour microenvironmental factors, hypoxia and abnormal pH homeostasis, were shown to increase the expression of carcinoembryonic antigen in cancer cells. In addition, the absence of acidic organelles was shown to induce mistargeting of CEA to the basolateral membrane in polarised cells. The abnormally neutral Golgi was found to interfere with the complex formation of carcinoembryonic antigen, a phenomenon recently associated with the apical sorting of other GPI-anchored proteins. Altogether these results emphasise the role of tumour-related factors – altered pH homeostasis and hypoxia – in the phenotypic changes of cancer cells.