Celine Heu

Publications (3)5.92 Total impact

• Article: A step further toward glyphosate-induced epidermal cell death: Involvement of mitochondrial and oxidative mechanisms.

  Celine Heu, Celine Elie-Caille, Virginie Mougey, Sophie Launay, Laurence Nicod
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  ABSTRACT: A deregulation of programmed cell death mechanisms in human epidermis leads to skin pathologies. We previously showed that glyphosate, an extensively used herbicide, provoked cytotoxic effects on cultured human keratinocytes, affecting their antioxidant capacities and impairing morphological and functional cell characteristics. The aim of the present study, carried out on the human epidermal cell line HaCaT, was to examine the part of apoptosis plays in the cytotoxic effects of glyphosate and the intracellular mechanisms involved in the apoptotic events. We have conducted different incubation periods to reveal the specific events in glyphosate-induced cell death. We observed an increase in the number of early apoptotic cells at a low cytotoxicity level (15%), and then, a decrease, in favor of late apoptotic and necrotic cell rates for more severe cytotoxicity conditions. At the same time, we showed that the glyphosate-induced mitochondrial membrane potential disruption could be a cause of apoptosis in keratinocyte cultures.
  Environmental toxicology and pharmacology. 03/2012; 34(2):144-153.
• Article: Glyphosate-induced stiffening of HaCaT keratinocytes, a Peak Force Tapping study on living cells.

  Celine Heu, Alexandre Berquand, Celine Elie-Caille, Laurence Nicod
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  ABSTRACT: The skin is the first physiological barrier, with a complex constitution, that provides defensive functions against multiple physical and chemical aggressions. Glyphosate is an extensively used herbicide that has been shown to increase the risk of cancer. Moreover there is increasing evidence suggesting that the mechanical phenotype plays an important role in malignant transformation. Atomic force microscopy (AFM) has emerged within the last decade as a powerful tool for providing a nanometer-scale resolution imaging of biological samples. Peak Force Tapping (PFT) is a newly released AFM-based investigation technique allowing extraction of chemical and mechanical properties from a wide range of samples at a relatively high speed and a high resolution. The present work uses the PFT technology to investigate HaCaT keratinocytes, a human epidermal cell line, and offers an original approach to study chemically-induced changes in the cellular mechanical properties under near-physiological conditions. These experiments indicate glyphosate induces cell membrane stiffening, and the appearance of cytoskeleton structures at a subcellular level, for low cytotoxic concentrations whereas cells exposed to IC50 (inhibitory concentration 50%) treatment exhibit control-like mechanical behavior despite obvious membrane damages. Quercetin, a well-known antioxidant, reverses the glyphosate-induced mechanical phenotype.
  Journal of Structural Biology 02/2012; 178(1):1-7. · 3.41 Impact Factor
• Article: Morphological damages of a glyphosate-treated human keratinocyte cell line revealed by a micro- to nanoscale microscopic investigation.

  Celine Elie-Caille, Celine Heu, Catherine Guyon, Laurence Nicod
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  ABSTRACT: Among the molecules to which the human skin is exposed, glyphosate is used as an herbicide. Glyphosate has been shown to induce in vitro cutaneous cytotoxic effects, concomitant with oxidative disorders. In this following study, we focused on dynamic events of the loss of HaCaT cell integrity appearing after a glyphosate treatment. In these conditions, we showed that glyphosate is able to disrupt HaCaT cells and to induce intracellular oxidative cascade. In this aim, we optimized the conditions of cell treatment playing on exposure time (from 24 h to 30 min), which directly modify the cell viability profile (glyphosate 50% inhibition concentration from 28 to 53 mM) and allow to track cells along the treatment as an "induction and visualization" process. The combination of atomic force and fluorescence microscopic approaches offered opportunities to lead in parallel an investigation of the membrane surface and of the intracellular disorders, through cytoskeleton, nuclear, and oxidative stress marker targeting. The originality of our approach relies on monitoring all events derived from oxidative stress in process and performed by simultaneous cytotoxic induction and nanoscale cell visualization. We revealed a transition from spread and globular to elongated cell morphology, with a drastic cell size reduction, after a dose- and time-dependent glyphosate treatment; a redistribution of cell surface protrusions was also pointed out. All these membrane damages, added to observations of disorganized cytoskeleton, condensed chromatin, and overproduction of oxidative reactive species, lead us to conclude that glyphosate acts in induction of apoptotic process.
  Cell Biology and Toxicology 08/2010; 26(4):331-9. · 2.51 Impact Factor