Estradiol exerts antiapoptotic effects in skeletal myoblasts via mitochondrial PTP and MnSOD.

17beta-Estradiol (E2) protects several non-reproductive tissues from apoptosis, including skeletal muscle. We have shown that E2 at physiological concentrations prevented apoptosis induced by H2O2 in C2C12 skeletal myoblasts. As we also demonstrated the presence of estrogen receptors in mitochondria, the present work was focused on the effects of E2 on this organelle. Specifically, we evaluated the actions of E2 on the mitochondrial permeability transition pore (MPTP) by the calcein-acetoxymethylester/cobalt method using fluorescence microscopy and flow cytometry. Pretreatment with E2 prevented MPTP opening induced by H2O2, which preceded loss of mitochondrial membrane potential. In addition, it was observed that H2O2 induced translocation of Bax to mitochondria; however, in the presence of the steroid this effect was abrogated suggesting that members of the Bcl-2 family may be regulated by E2 to exert an antiapoptotic effect. Moreover, E2 increased mitochondrial manganese superoxide dismutase protein expression and activity, as part of a mechanism activated by E2 that improved mitochondrial performance. Our results suggest a role of E2 in the regulation of apoptosis with a clear action at the mitochondrial level in C2C12 skeletal myoblast cells.Fil: la Colla, Anabela Belén. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vasconsuelo, Andrea Anahi. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Boland, Ricardo Leopoldo. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Mitochondrial dysfunction and epigenetics underlying the link between early-life nutrition and non-alcoholic fatty liver disease

Early-life malnutrition plays a critical role in fetal development and predispose to the appearance of metabolic diseases in later life, according to the concept of 'developmental programming'. Different types of early nutritional imbalances, including undernutrition, overnutrition or micronutrient deficiency have been related to long-term metabolic disorders. Accumulating evidence has demonstrated that disturbances in nutrition during the period of preconception, pregnancy and primary infancy can affect mitochondrial function and epigenetic mechanisms. Moreover, even though multiple mechanisms underlying non-alcoholic fatty liver disease (NAFLD) have been described, in the last years special attention has been given to mitochondrial dysfunction and epigenetic alterations. Mitochondria play a key role in cellular metabolic functions. Dysfunctional mitochondria contribute to oxidative stress, insulin resistance and inflammation. Epigenetic mechanisms have been related to alterations in genes involved in lipid metabolism, fibrogenesis, inflammation and tumorigenesis. In accordance, studies have reported that mitochondrial dysfunction and epigenetics linked to early-life nutrition can be important contributing factors in the pathogenesis of NAFLD. In this review, we summarize the current understanding of the interplay between mitochondrial dysfunction, epigenetics and nutrition during early life, which is relevant to developmental programming of NAFLD.Fil: la Colla, Anabela Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Camara, Carolina Anahí. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; ArgentinaFil: Campisano, Sabrina Edith. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; ArgentinaFil: Chisari, Andrea Nancy. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentin

Interplay between early-life malnutrition, epigenetic modulation of the immune function and liver diseases

Early-life nutrition plays a critical role in fetal growth and development. Food intake absence and excess are the two main types of energy malnutrition that predispose to the appearance of diseases in adulthood, according to the hypothesis of 'developmental origins of health and disease'. Epidemiological data have shown an association between early-life malnutrition and the metabolic syndrome in later life. Evidence has also demonstrated that nutrition during this period of life can affect the development of the immune system through epigenetic mechanisms. Thus, epigenetics has an essential role in the complex interplay between environmental factors and genetics. Altogether, this leads to the inflammatory response that is commonly seen in non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome. In conjunction, DNA methylation, covalent modification of histones and the expression of non-coding RNA are the epigenetic phenomena that affect inflammatory processes in the context of NAFLD. Here, we highlight current understanding of the mechanisms underlying developmental programming of NAFLD linked to epigenetic modulation of the immune system and environmental factors, such as malnutrition.Fil: Campisano, Sabrina Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; ArgentinaFil: la Colla, Anabela Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; ArgentinaFil: Echarte, Stella Maris. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; ArgentinaFil: Chisari, Andrea Nancy. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentin

High passage numbers induce resistance to apoptosis in C2C12 muscle cells

Cell lines with high passage numbers exhibit alterations in cell Morphology and functions. In the present work, C2C12 skeletal muscle cells with either low (60) passage numbers (identified as l-C2C12 or h-C2C12, respectively) were used to investigate the apoptotic response to H2O2 as a function of culture age h-C2C12. We found that older cultures (h-C2C12 group) were depleted of mitochondrial DNA (mtDNA). When we analyzed the behavior of Bad, Bax, caspase-3 and mitochondrial transmembrane potential, we observed that cells in the h-C2C12 group were resistant to H2O2 induction of apoptosis. We propose serially cultured C2C12 cells as a refractory model to H2O2-induced apoptosis. In addition, the data obtained in this work suggest that mtDNA is required for apoptotic cell death in skeletal muscle C2C12 cells.Fil: Pronsato, Lucía. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Bahia Blanca; Argentina;Fil: la Colla, Anabela Belén. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Laboratorio de Química Biológica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Bahia Blanca; Argentina;Fil: Ronda, Ana Carolina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Cátedra de Química Biológica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Bahia Blanca; Argentina;Fil: Milanesi, Lorena Magdalena. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Laboratorio de Química Biológica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Bahia Blanca; Argentina;Fil: Boland, Ricardo Leopoldo. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Bahia Blanca; Argentina;Fil: Vasconsuelo, Andrea Anahi. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Laboratorio de Química Biológica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Bahia Blanca; Argentina

El 17β-Estradiol y la Testosterona protegen a las mitocondrias contra el estrés oxidativo en Células del Músculo Esquelético

En trabajos previos demostramos que la testosterona (T) y el 17β-estradiol (E2) protegen a las células musculares C2C12 de la apoptosis inducida por peróxido de hidrógeno (H2O2). Conjuntamente evidenciamos la existencia de receptores de estrógenos y andrógenos en las mitocondrias. El presente trabajo se ha centrado en caracterizar los efectos de ambos esteroides en esta organela, que conducen a la supervivencia celular. Específicamente, se evaluaron las acciones de T y E2 sobre el potencial de membrana mitocondrial con el colorante JC-1 y sobre el poro de permeabilidad transitoria mitocondrial (MPTP) mediante el método de calcein-acetoxymethylester/cobalt, utilizando microscopía de fluorescencia y citometría de flujo. Demostramos que T y E2 previenen la apertura del MPTP y la pérdida de potencial de membrana mitocondrial inducidas por H2O2. Además, observamos que el H2O2 aumenta los niveles de expresión proteica del canal aniónico dependiente de voltaje (VDAC) e induce la translocación de Bax a mitocondria. Sin embargo, en presencia de las hormonas la translocación de Bax fue inhibida lo cual sugiere que los miembros de la familia Bcl -2 pueden ser regulados por E2 y T. Los eventos moleculares desencadenados por E2 y T a nivel mitocondrial se reflejaron en la morfología de las organelas. El análisis microscópico de las células C2C12 y cultivos primarios de músculo esquelético de ratón, mediante tinciones con verde de Jano y Mitotracker reveló un efecto protector de los esteroides contra el daño por estrés oxidativo inhibiendo la redistribución y picnosis mitocondrial.We have previously shown that testosterone (T) and 17β-estradiol (E2) protect C2C12 muscle cells against apoptosis induced by hydrogen peroxide (H2O2). Since we also showed the presence of estrogen and androgen Receptors in mitochondria, this work was focused on the effects of both steroids on this organelle, which result in cellular survival. Specifically, we evaluated the actions of T and E2 on the mitochondrial membrane potential with JC-1 dye and on the mitochondrial permeability transition pore (MPTP) by the calceinacetoxymethylester (AM)/cobalt method, using fluorescence microscopy and flow cytometry. We demonstrated that T and E2 prevent MPTP opening and the loss of mitochondrial membrane potential induced by H2O2. In addition, it was observed that H2O2 increase voltage-dependent anion channel (VDAC) protein expression levels and induce translocation of Bax to mitochondria. However, in the presence of the steroids Bax translocation was abrogated suggesting that members of the Bcl-2 family may be regulated by E2 and T. The observed effects triggered by E2 and T were reflected on mitochondrial morphology. Microscopic analysis of C2C12 cells and primary cultures of mouse skeletal muscle, with Janus Green and Mitotracker staining revealed a protective effect of the steroids against oxidative stress damage which included mitochondrial redistribution and pyknosis of the organelle.Fil: la Colla, Anabela Belén. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Pronsato, Lucía. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico Bahia Blanca. Instituto de Ciencias Biologicas y Biomedicas del Sur; ArgentinaFil: Ronda, Ana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto Argentino de Oceanografía (i); Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Milanesi, Lorena Magdalena. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico Bahia Blanca. Instituto de Ciencias Biologicas y Biomedicas del Sur; ArgentinaFil: Vasconsuelo, Andrea Anahi. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico Bahia Blanca. Instituto de Ciencias Biologicas y Biomedicas del Sur; ArgentinaFil: Boland, Ricardo Leopoldo. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico Bahia Blanca. Instituto de Ciencias Biologicas y Biomedicas del Sur; Argentin

17β-Estradiol Protects Skeletal Myoblasts From Apoptosis Through p53, Bcl-2, and FoxO Families

17β-Estradiol (E2) protects several nonreproductive tissues from apoptosis, including skeletal muscle. Previously, we showed that E2 at physiological concentrations prevented apoptosis induced by H2O2 in skeletal myoblasts, reverting PKCδ, JNK, and p66Shc activation and exerting a beneficial action over mitochondria. Since genomic actions underlying the regulation of nuclear gene transcription are a common property of this steroid, the present work characterizes the transcriptional activity modulated by E2 to exert its antiapoptotic effect. We report that E2 protects skeletal myoblasts against apoptosis induced by H2O2 modulating p53 and FoxO transcription factors and then their target genes Bcl-2, Bim, Puma, PERP, and MDM2, without affecting Noxa gene. The results presented in this work support the notion that the transcription factors FoxO and p53 coordinate apoptosis in C2C12 cells, and deepens our knowledge about a putative molecular mechanism by which E2 exerts beneficial effects against oxidative stress in skeletal myoblasts.Fil: la Colla, Anabela Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Vasconsuelo, Andrea Anahi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Milanesi, Lorena Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Pronsato, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentin

Testosterone modulates FoxO3a and p53-related genes to protect C2C12 skeletal muscle cells against apoptosis

The loss of muscle mass and strength with aging, sarcopenia, is a prevalent condition among the elderly, associated with skeletal muscle dysfunction and enhanced muscle cell apoptosis. We have previously demonstrated that testosterone protects against H2O2-induced apoptosis in C2C12 muscle cells, at different levels: morphological, biochemical and molecular. Since we have observed that testosterone reduces p-p53 and maintains the inactive state of FoxO3a transcription factor, induced by H2O2, we analyzed if the hormone was exerting its antiapoptotic effect at transcriptional level, by modulating pro and antiapoptotic genes associated to them. We detected the upregulation of the proapoptotic genes Puma, PERP and Bim, and MDM2 in response to H2O2 at different periods of the apoptotic process, and the downregulation of the antiapoptotic gene Bcl-2, whereas testosterone was able to modulate and counteract H2O2 effects. Furthermore, ERK and JNK kinases have been demonstrated to be linked to FoxO3a phosphorylation and thus its subcellular distribution. This work show some transcription level components, upstream of the classical apoptotic pathway, that are activated during oxidative stress and that are points where testosterone exerts its protective action against apoptosis, exposing some of the puzzle pieces of the intricate network that aged skeletal muscle apoptosis represents.Fil: Pronsato, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Milanesi, Lorena Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Vasconsuelo, Andrea Anahi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: la Colla, Anabela Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentin

17-betaEstradiol and testosterone in sarcopenia: Role of satellite cells

The loss of muscle mass and strength with aging, referred to as sarcopenia, is a prevalent condition among the elderly. Although the molecular mechanisms underlying sarcopenia are unclear, evidence suggests that an age-related acceleration of myocyte loss via apoptosis might be responsible for muscle perfomance decline. Interestingly, sarcopenia has been associated to a deficit of sex hormones which decrease upon aging. The skeletal muscle ability to repair and regenerate itself would not be possible without satellite cells, a subpopulation of cells that remain quiescent throughout life. They are activated in response to stress, enabling them to guide skeletal muscle regeneration. Thus, these cells could be a key factor to overcome sarcopenia. Of importance, satellite cells are 17β-estradiol (E2) and testosterone (T) targets. In this review, we summarize potential mechanisms through which these hormones regulate satellite cells activation during skeletal muscle regeneration in the elderly. The advance in its understanding will help to the development of potential therapeutic agents to alleviate and treat sarcopenia and other related myophaties.Fil: la Colla, Anabela Belén. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Ciencias Biologicas y Biomedicas del Sur; ArgentinaFil: Pronsato, Lucía. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Ciencias Biologicas y Biomedicas del Sur; ArgentinaFil: Milanesi, Lorena Magdalena. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Ciencias Biologicas y Biomedicas del Sur; ArgentinaFil: Vasconsuelo, Andrea Anahi. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Ciencias Biologicas y Biomedicas del Sur; Argentin

The subcellular localization and physiological roles of estrogen receptors α and β in classical and non-classical tissues

It is now firmly established that estrogens elicit a variety of rapid effects in many tissues in addition to their delayed action on gene expression in the cell nucleus. Moreover, the classic estrogen receptors have been shown to act on signaling cascades. In this chapter we summarize various aspects of estradiol signaling, with special emphasis in the fast action of the hormone. We first concisely describe the traditional mechanism of action of the steroid and include new data about receptor structural features, its cellular localization, targets and role in classical and non-classical tissues. Moreover, we have compared the structure of the different estrogen receptors and how they are activated by distinct mechanisms. The likely interactions of non-classical estrogen receptors with other local proteins and their relationships with rapid signaling pathways triggered by estradiol are also discussed.Fil: Pronsato, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: la Colla, Anabela Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Milanesi, Lorena Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Vasconsuelo, Andrea Anahi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentin

Effect of testosterone on the regulation of protein and gene expression related to oxidative stress damage in C2C12 cells

The loss of muscle mass and strength with aging, also referred to as sarcopenia, is a prevalent condition among the elderly, associated with a deficit of sex hormones. In our previous works we have demonstrated that testosterone protects against H2O2-induced apoptosis in C2C12 at different levels: morphological, physiological, biochemical andmolecular. In the present study we evaluated some of the components upstream of the classical apoptotic pathway which could trigger this response, the expression levels of genes related to these pathways and the role of the hormone during these events. By Western blot and immunocytochemistry, we observed that H2O2 treatment induces theactivation of p53 in a time-dependent way. Phosphorylation of p53 induced by H2O2 is reduced by testosterone treatment prior to H2O2. One of the ways that p53 induces apoptosis is through p66Shc activation, an adaptor proteinwhichamplifies the generation of mitochondrial hydrogen peroxide. Our studies showed that hormone incubation prior to H2O2 reduces p66Shc activation and its mitochondrial localization. Furthermore, testosterone diminished JNK phosphorylation induced by the apoptotic agent. So JNKcould be acting as a p66Shc activator, since pretreatment with a JNK inhibitor decreased the phosphorylation not only of JNK but also of p66Shc. Finally, mRNA levels of different pro and anti-apoptotic genes were determined by real time PCR, during the apoptotic stimuli in the presence or absence of the hormone, showing that testosterone has opposite effects over gene expression to H2O2. Testosterone would therefore favor the expression of genes related to proliferation and survival respect of those associated to apoptosis.Fil: Pronsato, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: la Colla, Anabela Belén. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Vasconsuelo, Andrea Anahi. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Boland, Ricardo Leopoldo. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Milanesi, Lorena Magdalena. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentin