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Rodolfo-Metalpa R.,International Atomic Energy Agency | Martin S.,French National Center for Scientific Research | Ferrier-Pages C.,Center Scientifique Of Monaco | Gattuso J.-P.,French National Center for Scientific Research | Gattuso J.-P.,University Pierre and Marie Curie
Biogeosciences | Year: 2010

Atmospheric CO 2 partial pressure (pCO 2) is expected to increase to 700 μatm or more by the end of the present century. Anthropogenic CO 2 is absorbed by the oceans, leading to decreases in pH and the CaCO 3 saturation state (Ω) of the seawater. Elevated pCO 2 was shown to drastically decrease calcification rates in tropical zooxanthellate corals. Here we show, using the Mediterranean zooxanthellate coral Cladocora caespitosa, that an increase in pCO 2, in the range predicted for 2100, does not reduce its calcification rate. Therefore, the conventional belief that calcification rates will be affected by ocean acidification may not be widespread in temperate corals. Seasonal change in temperature is the predominant factor controlling photosynthesis, respiration, calcification and symbiont density. An increase in pCO 2, alone or in combination with elevated temperature, had no significant effect on photosynthesis, photosynthetic efficiency and calcification. The lack of sensitivity C. caespitosa to elevated pCO 2 might be due to its slow growth rates, which seem to be more dependent on temperature than on the saturation state of calcium carbonate in the range projected for the end of the century.

Parks S.K.,University of Nice Sophia Antipolis | Mazure N.M.,University of Nice Sophia Antipolis | Counillon L.,University of Nice Sophia Antipolis | Pouyssegur J.,University of Nice Sophia Antipolis | Pouyssegur J.,Center Scientifique Of Monaco
Journal of Cellular Physiology | Year: 2013

The efficacy of targeting pH disruption to induce cell death in the acidic and hypoxic tumor microenvironment continues to be assessed. Here we analyzed the impact of varying levels of hypoxia in acidic conditions on fibroblast and tumor cell survival. Across all cell lines tested, hypoxia (1% O2) provided protection against acidosis induced cell death compared to normoxia. Meanwhile severe hypoxia (0.1% O2) removed this protection and in some cases exacerbated acidosis-induced cell death. Differential survival between cell types during external acidosis correlated with their respective intracellular pH regulating capabilities. Cellular ATP measurements were conducted to determine their contribution to cell survival under these combined stresses. In general, hypoxia (1% O2) maintained elevated ATP levels in acidic conditions while severe hypoxia did not. To further explore this interaction we combined acidosis with ATP depletion using 2-deoxyglucose and observed an enhanced rate of cell mortality. Striking results were also observed with hypoxia providing protection against cell death in spite of a severe metabolic stress induced by a combination of acidosis and oligomycin. Finally, we demonstrated that both HIF1α and HIF2α expression were drastically reduced in hypoxic and acidic conditions indicating a sensitivity of this protein to cellular pH conditions. This knockdown of HIF expression by acidosis has implications for the development of therapies targeting the disruption of cellular pH regulation. Our results reinforce the proof of concept that acidosis and metabolic disruption affecting ATP levels could be exploited as a tumor cell killing strategy. © 2013 Wiley Periodicals, Inc.

Marchiq I.,University of Nice Sophia Antipolis | Pouyssegur J.,University of Nice Sophia Antipolis | Pouyssegur J.,Center Scientifique Of Monaco
Journal of Molecular Medicine | Year: 2016

Since Otto Warburg reported the ‘addiction’ of cancer cells to fermentative glycolysis, a metabolic pathway that provides energy and building blocks, thousands of studies have shed new light on the molecular mechanisms contributing to altered cancer metabolism. Hypoxia, through hypoxia-inducible factors (HIFs), in addition to oncogenes activation and loss of tumour suppressors constitute major regulators of not only the “Warburg effect” but also many other metabolic pathways such as glutaminolysis. Enhanced glucose and glutamine catabolism has become a recognised feature of cancer cells, leading to accumulation of metabolites in the tumour microenvironment, which offers growth advantages to tumours. Among these metabolites, lactic acid, besides imposing an acidic stress, is emerging as a key signalling molecule that plays a pivotal role in cancer cell migration, angiogenesis, immune escape and metastasis. Although interest in lactate for cancer development only appeared recently, pharmacological molecules blocking its metabolism are already in phase I/II clinical trials. Here, we review the metabolic pathways generating lactate, and we discuss the rationale for targeting lactic acid transporter complexes for the development of efficient and selective anticancer therapies. © 2015, The Author(s).

Davy S.K.,Victoria University of Wellington | Allemand D.,Center Scientifique Of Monaco | Weis V.M.,Oregon State University
Microbiology and Molecular Biology Reviews | Year: 2012

The symbiosis between cnidarians (e.g., corals or sea anemones) and intracellular dinoflagellate algae of the genus Symbiodinium is of immense ecological importance. In particular, this symbiosis promotes the growth and survival of reef corals in nutrient-poor tropical waters; indeed, coral reefs could not exist without this symbiosis. However, our fundamental understanding of the cnidarian-dinoflagellate symbiosis and of its links to coral calcification remains poor. Here we review what we currently know about the cell biology of cnidariandinoflagellate symbiosis. In doing so, we aim to refocus attention on fundamental cellular aspects that have been somewhat neglected since the early to mid-1980s, when a more ecological approach began to dominate. We review the four major processes that we believe underlie the various phases of establishment and persistence in the cnidarian/coral-dinoflagellate symbiosis: (i) recognition and phagocytosis, (ii) regulation of host-symbiont biomass, (iii) metabolic exchange and nutrient trafficking, and (iv) calcification. Where appropriate, we draw upon examples from a range of cnidarian-alga symbioses, including the symbiosis between green Hydra and its intracellular chlorophyte symbiont, which has considerable potential to inform our understanding of the cnidarian-dinoflagellate symbiosis. Ultimately, we provide a comprehensive overview of the history of the field, its current status, and where it should be going in the future. Copyright © 2012, American Society for Microbiology. All Rights Reserved.

Picco V.,Center Scientifique Of Monaco | Pages G.,University of Nice Sophia Antipolis
Genes and Cancer | Year: 2013

The activity of c-Jun N-terminal kinase (JNK) was initially described as ultraviolet- and oncogene-induced kinase activity on c-Jun. Shortly after this initial discovery, JNK activation was reported for a wider variety of DNA-damaging agents, including γ-irradiation and chemotherapeutic compounds. As the DNA damage response mechanisms were progressively uncovered, the mechanisms governing the activation of JNK upon genotoxic stresses became better understood. In particular, a recent set of papers links the physical breakage in DNA, the activation of the transcription factor NF-κB, the secretion of TNF-α, and an autocrine activation of the JNK pathway. In this review, we will focus on the pathway that is initiated by a physical break in the DNA helix, leading to JNK activation and the resultant cellular consequences. The implications of these findings will be discussed in the context of cancer therapy with DNA-damaging agents. © The Author(s) 2013.

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