Bruzzese Laurie, Rostain Jean-Claude, Née Laëtitia, Condo Jocelyne, Mottola Giovanna, Adjriou Nabil, Mercier Laurence, Berge-Lefranc Jean-Louis, Fromonot Julien, Kipson Nathalie, Lucciano Michel, Durand-Gorde Josée-Martine, Jammes Yves, Guieu Régis, Ruf Jean, Fenouillet Emmanuel
UMR MD2, Institute of Biological Research, French Defense Ministry (IRBA), Aix Marseille University, Marseille, France;
UMR MD2, Institute of Biological Research, French Defense Ministry (IRBA), Aix Marseille University, Marseille, France; Department of Anesthesia and Intensive Care, Timone University Hospital, Marseille, France;
J Appl Physiol (1985). 2015 Jul 15;119(2):140-7. doi: 10.1152/japplphysiol.00223.2015. Epub 2015 May 21.
The nucleoside adenosine acts on the nervous and cardiovascular systems via the A2A receptor (A2AR). In response to oxygen level in tissues, adenosine plasma concentration is regulated in particular via its synthesis by CD73 and via its degradation by adenosine deaminase (ADA). The cell-surface endopeptidase CD26 controls the concentration of vasoactive and antioxidant peptides and hence regulates the oxygen supply to tissues and oxidative stress response. Although overexpression of adenosine, CD73, ADA, A2AR, and CD26 in response to hypoxia is well documented, the effects of hyperoxic and hyperbaric conditions on these elements deserve further consideration. Rats and a murine Chem-3 cell line that expresses A2AR were exposed to 0.21 bar O2, 0.79 bar N2 (terrestrial conditions; normoxia); 1 bar O2 (hyperoxia); 2 bar O2 (hyperbaric hyperoxia); 0.21 bar O2, 1.79 bar N2 (hyperbaria). Adenosine plasma concentration, CD73, ADA, A2AR expression, and CD26 activity were addressed in vivo, and cAMP production was addressed in cellulo. For in vivo conditions, 1) hyperoxia decreased adenosine plasma level and T cell surface CD26 activity, whereas it increased CD73 expression and ADA level; 2) hyperbaric hyperoxia tended to amplify the trend; and 3) hyperbaria alone lacked significant influence on these parameters. In the brain and in cellulo, 1) hyperoxia decreased A2AR expression; 2) hyperbaric hyperoxia amplified the trend; and 3) hyperbaria alone exhibited the strongest effect. We found a similar pattern regarding both A2AR mRNA synthesis in the brain and cAMP production in Chem-3 cells. Thus a high oxygen level tended to downregulate the adenosinergic pathway and CD26 activity. Hyperbaria alone affected only A2AR expression and cAMP production. We discuss how such mechanisms triggered by hyperoxygenation can limit, through vasoconstriction, the oxygen supply to tissues and the production of reactive oxygen species.
核苷腺苷通过A2A受体（A2AR）作用于神经和心血管系统。响应组织中的氧水平，腺苷血浆浓度尤其通过CD73的合成及其通过腺苷脱氨酶（ADA）的降解来调节。细胞表面内肽酶CD26控制血管活性和抗氧化肽的浓度，从而调节组织的氧供应和氧化应激反应。尽管低氧条件下腺苷、CD73、ADA、A2AR和CD26的过表达已有充分记录，但高氧和高压条件对这些因素的影响值得进一步研究。将大鼠和表达A2AR的小鼠Chem-3细胞系暴露于0.21 bar O2、0.79 bar N2（陆地条件；常氧）；1 bar O2（高氧）；2 bar O2（高压高氧）；0.21 bar O2、1.79 bar N2（高压）。在体内研究了腺苷血浆浓度、CD73、ADA、A2AR表达和CD26活性，在细胞内研究了cAMP产生。对于体内条件，1）高氧降低了腺苷血浆水平和T细胞表面CD26活性，而增加了CD73表达和ADA水平；2）高压高氧倾向于放大这种趋势；3）单独高压对这些参数没有显著影响。在脑内和细胞内，1）高氧降低了A2AR表达；2）高压高氧放大了这种趋势；3）单独高压表现出最强的作用。我们在脑内A2AR mRNA合成和Chem-3细胞内cAMP产生方面发现了类似模式。因此，高氧水平倾向于下调腺苷能途径和CD26活性。单独高压仅影响A2AR表达和cAMP产生。我们讨论了这种由高氧引发的机制如何通过血管收缩限制组织的氧供应和活性氧的产生。
