ORALS

SESSION: OxidativeThuAM-R5	Intl. Symp. on Oxidative Stress for Sustainable Development of Human Beings
Thu Oct, 24 2019 / Room: Zeus (55/Mezz. F)
Session Chairs: Christian Amatore; HARUHIKO INUFUSA; Session Monitor: TBA

12:10: [OxidativeThuAM03]
Understanding Oxidative Stress in Brain with Ultramicroelectrodes: Implications for a Possible Mechanism of Alzheimer Disease
Christian Amatore¹ ; ¹CNRS & PSL, French Acad. of Sci. and Xiamen University, Paris, France;
Paper Id: 323 [Abstract]

Oxidative stress is an essential metabolic outcome in aerobic organisms due to the activity of the mitochondria in providing the basic energy of cells or during the operation of several enzymatic pools. It also serves to regulate the size and shape of organs or restructure them during foetal development by apoptosis. Oxidative stress is also indispensable to the immune system by allowing macrophages to eliminate virus, bacteria and impaired or dead cells through phagocytosis [1]. In fact, no aerobic organism could live without oxidative stress: a fact that explains why evolution maintained such unsafe mechanisms in aerobic organisms. They are, however, associated to highly negative issues. Indeed, oxidative stress mechanisms provide a variety of life-harmful radicals and species called generically Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) whose fluxes need to be finely controlled to avoid the destruction of most organic molecules (e.g., lipids in cell membranes, enzymes, etc.) and biological molecules (DNA, proteins, etc.) in cells. Thus, under normal conditions, a panoply of antioxidants and enzymatic systems ensures a fine homeostatic balance. Rupture of this delicate balance, however, is frequent and may provoke severe damages leading to human pathologies (aging, cancers, AIDS, hearth and brain strokes, Parkinson and Alzheimer’ diseases, etc.). Using platinized carbon fiber ultramicroelectrodes, we could establish the composition of primary oxidative stress in macrophages [1, 2] and characterize the nature of functional hyperemia in the brain [3]. This led us to formulate an alternative hypothesis about the onset of Alzheimer disease when Amyloid-β and ascorbate molecules are present [4, 5].

References:
1. K. Hu, Y. Li, S.A. Rotenberg, C. Amatore, M.V. Mirkin. J. Am. Chem. Soc., 141, 2019, 4564-4568.
2. C Amatore, S. Arbault, M. Guille, F. Lemaître. Chem. Rev., 108, 2008, 2585–2621.
3. C. Amatore, S. Arbault, C. Bouton, K. Coffi, J.-C. Drapier, H. Ghandour, Y. Tong. ChemBioChem, 7, 2006, 653-661.
4. R. Giacovazzi, I. Ciofini, L. Rao, C. Adamo, C. Amatore, Phys. Chem. Phys. Chem. (PCCP), 16, 2014, 10169-10174.
5. L. Lai, C. Zhao, M. Su, X. Li, X. Liu, H. Jiang, C. Amatore, X.M. Wang. Biomater. Sc., 4, 2016, 1085-1091.

SESSION: OxidativeThuPM2-R5	Intl. Symp. on Oxidative Stress for Sustainable Development of Human Beings
Thu Oct, 24 2019 / Room: Zeus (55/Mezz. F)
Session Chairs: Alexander Oleinick; Harry van Goor; Session Monitor: TBA

16:20: [OxidativeThuPM210]
Theoretical Aspects of Reactive Oxygen/Nitrogen Species Homeostasis inside Macrophages during Phagocytosis Monitored at Nanoelectrodes
Alexander Oleinick¹ ; Xin-wei Zhang² ; Irina Svir³ ; Christian Amatore⁴ ; Wei-hua Huang⁵ ; ¹CNRS-ENS-SU UMR 8640 PASTEUR, CNRS, Paris, France; ²Key Laboratory of Analytical Chemistry for Biology and Medicine, College of Chemistry and Molecular Sciences, Wuhan, China; ³Ecole Normale Superieure, Department Chemistry, PARIS, France; ⁴CNRS & PSL, French Acad. of Sci. and Xiamen University, Paris, France; ⁵Wuhan University, Wuhan, China;
Paper Id: 322 [Abstract]

Traffic of the lipid-enclosed compartments (vesicles, endosomes, phagosomes etc.) within the cell is extremely important for sustaining cell life and allowing the cell to perform its function. These lipid bilayer bound organelles deliver their cargo through bilayer fusion with the other organelles or with the plasma membrane. In the case when the release of the cargo molecule is controlled only by diffusion, we have shown earlier for the case of vesicular exocytosis that emptying of such organelles occurs exponentially and the rate of the exponential decay is controlled by the size of the fusion pore [1]. The generality of the assumptions made for model derivation, as well as for laws underlying this model, suggest that the assumptions can be applied to a vast variety of cases. This can be done independently if organelles fuse with another part like the cellular membrane or electrode (like in vesicle impact electrochemical cytometry), etc. Moreover, being able to describe mass transport of the cargo molecules inside or out of the organelle allow one to characterize various physicochemical processes occurring within the organelle [2]. In particular, relevantly adapted models were applied to the case of the detection with the platinized carbon nanoelectrode of the reactive oxygen/nitrogen species (ROS/RNS) produced by macrophages inside their phagolysosomes (more on the experiment will be presented in Prof. Wei-Hua Huang's talk) [3]. Modelling the oxidation and mass transport of the ROS/RNS towards the nanoelectrode and comparison with experimental data evidenced <u>for the first time</u> that the consumption of ROS/RNS by their oxidation at the nanoelectrode surface stimulates the production of significant ROS/RNS amounts inside phagolysosomes, i.e., proved the very existence of a ROS/RNS homeostasis during phagocytosis. The homeostatic production rates of ROS/RNS inside individual phagolysosomes were quantified by employing the developed theory [3]. These results allowed measuring the long-time postulated ROS/RNS homeostasis within the phagolysosome, its kinetics and its efficiency. ROS/RNS concentrations may then be maintained at sufficiently high levels to sustain proper pathogen digestion rates without endangering the macrophage internal structures [3].

References:
1. A. Oleinick, I. Svir, C. Amatore. Proc. R. Soc. A, 473, 2017, 20160684.\n2. A. Oleinick, I. Svir, W.-H. Huang, C. Amatore, in preparation.\n3. X.-W. Zhang, A. Oleinick, H. Jiang, Q.-L. Liao, Q.-F. Qiu, I. Svir, Y.-L. Liu, C. Amatore, W.-H. Huang. Angew. Chem. Ind. Ed., 58, 2019, 7753-7756.