Erythropoietin and the use of a transgenic model of erythropoietin-deficient mice.

Despite its well-known role in red blood cell production, it is now accepted that erythropoietin (Epo) has other physiological functions. Epo and its receptors are expressed in many tissues, such as the brain and heart. The presence of Epo/Epo receptors in these organs suggests other roles than those usually assigned to this protein.

Regulation of myogenesis by environmental hypoxia.

In aerobic organisms, oxygen is a critical factor for tissue and organ morphogenesis from embryonic development throughout the adult life. It regulates various intracellular pathways involved in cellular metabolism, proliferation, cell survival and fate. Organisms or tissues rapidly respond to changes in oxygen availability by activating complex signalling networks, which culminate in the control of mRNA translation and/or gene expression.

Oxygen modulates the glutathione peroxidase activity during the L6 myoblast early differentiation process.

Aim: This work aims to study the regulation of the glutathione peroxidase and catalase activities in myoblasts from the L6 line exposed to 21%, 5% and 1% O2 during the cell differentiation.

Material And Methods: Rat L6 myoblasts were grown in 1%, 5% or 21% O2 in the presence or absence of N-acetyl cysteine. The cell proliferation was evaluated by determining the doubling time and kinetics of cultures by counting cells.

The translational repressor 4E-BP mediates hypoxia-induced defects in myotome cells.

Cell growth, proliferation, differentiation and survival are influenced by the availability of oxygen. The effect of hypoxia on embryonic cells and the underlying molecular mechanisms to maintain cellular viability are still poorly understood. In this study, we show that hypoxia during Xenopus embryogenesis rapidly leads to a significant developmental delay and to cell apoptosis after prolonged exposure.

Hypoxia transiently affects skeletal muscle hypertrophy in a functional overload model.

Hypoxia induces a loss of skeletal muscle mass, but the signaling pathways and molecular mechanisms involved remain poorly understood. We hypothesized that hypoxia could impair skeletal muscle hypertrophy induced by functional overload (Ov). To test this hypothesis, plantaris muscles were overloaded during 5, 12, and 56 days in female rats exposed to hypobaric hypoxia (5,500 m), and then, we examined the responses of specific signaling pathways involved in protein synthesis (Akt/mTOR) and breakdown (atrogenes).

Epo is relevant neither for microvascular formation nor for the new formation and maintenance of mice skeletal muscle fibres in both normoxia and hypoxia.

Erythropoietin (Epo) and vascular growth factor (VEGF) are known to be involved in the regulation of cellular activity when oxygen transport is reduced as in anaemia or hypoxic conditions. Because it has been suggested that Epo could play a role in skeletal muscle development, regeneration, and angiogenesis, we aimed to assess Epo deficiency in both normoxia and hypoxia by using an Epo-deficient transgenic mouse model (Epo-TAg(h)). Histoimmunology, ELISA and real time RT-PCR did not show any muscle fiber atrophy or accumulation of active HIF-1alpha but an improvement of microvessel network and an upregulation of VEGFR2 mRNA in Epo-deficient gastrocnemius compared with Wild-Type one.

Skeletal muscle intrinsic functional properties are preserved in a model of erythropoietin deficient mice exposed to hypoxia.

Erythropoietin (Epo)-induced polycythemia is the main factor of adaptation to hypoxia. In this study, we analysed the effects of Epo deficiency on intrinsic functional properties of slow and fast twitch muscles in a model of erythropoietin deficient mice (Epo-TAg(h)) exposed to hypoxia. We hypothesised that Epo deficiency would be deleterious for skeletal muscle structure and phenotype, which could change its functional properties and alters the adaptive response to ambient hypoxia.

Interaction between hypoxia and training on NIRS signal during exercise: contribution of a mathematical model.

Acute exposure to hypoxia provokes a decrease in peak oxygen consumption ( V(O)(2peak)). At and above 4000 m, the decrease in V(O)(2peak) is greater than expected from the decrease in arterial oxygen content (C(a)O(2)) suggesting the participation of other factors. We hypothesized that O(2) transfer within the active muscle may play a role.

Non-invasive evaluation of the capillary recruitment in the human muscle during exercise in hypoxia.

This study proposes a non-invasive evaluation of capillary recruitment in human muscle from resting state to maximal exercise while under hypoxic conditions. Our work is based on the analysis of oxygen transport variables measured during incremental exercise in endurance-trained men (n=8) and in their sedentary counterparts (n=8). Maximal exercise tests were performed on a cycloergometer in normoxia and at three simulated normobaric levels of hypoxia (altitude equivalent to 1000, 2500 and 4500 m).

Cerebral adaptations to chronic anemia in a model of erythropoietin-deficient mice exposed to hypoxia.

Anemia and hypoxia in rats result in an increase in factors potentially involved in cerebral angiogenesis. Therefore, the aim of this study was to assess the effect of chronic anemia and/or chronic hypoxia on cerebral cellular responses and angiogenesis in wild-type and anemic transgenic mice. These studies were done in erythropoietin-deficient mice (Epo-TAg(h)) in normoxia and following acute (one day) and chronic (14 days, barometric pressure = 420 mmHg) hypoxia.

In vivo analyzes of dystroglycan function during somitogenesis in Xenopus laevis.

Dystroglycan (Dg) is a cell adhesion receptor for laminin that has been reported to play a role in skeletal muscle cell stability, cytoskeletal organization, cell polarity, and signaling. Here we show that Dg is expressed at both the notochord/somite and the intersomitic boundaries, where laminin and fibronectin are accumulated during somitogenesis. Inhibition of Dg function with morpholino antisense oligonucleotides or a dominant negative mutant results in the normal segmentation of the presomitic mesoderm but affects the number, the size, and the integrity of somites.

Determinant factors of the decrease in aerobic performance in moderate acute hypoxia in women endurance athletes.

The purpose of this study was to evaluate the limiting factors of maximal aerobic performance in endurance trained (TW) and sedentary (UW) women. Subjects performed four incremental tests on a cycle ergometer at sea level and in normobaric hypoxia corresponding to 1000, 2500 and 4500 m. Maximal oxygen uptake decrement (Delta VO2 max) was larger in TW at each altitude.

Determinants of maximal oxygen uptake in moderate acute hypoxia in endurance athletes.

The factors determining maximal oxygen consumption were explored in eight endurance trained subjects (TS) and eight untrained subjects (US) exposed to moderate acute normobaric hypoxia. Subjects performed maximal incremental tests at sea level and simulated altitudes (1,000, 2,500, 4,500 m). Heart rate (HR), stroke volume (SV), cardiac output (.

Pyruvate shuttle in muscle cells: high-affinity pyruvate transport sites insensitive to trans-lactate efflux.

The specificity of the transport mechanisms for pyruvate and lactate and their sensitivity to inhibitors were studied in L6 skeletal muscle cells. Trans- and cis-lactate effects on pyruvate transport kinetic parameters were examined. Pyruvate and lactate were transported by a multisite carrier system, i.