title: A functional interplay between 5-lipoxygenase and μ-calpain affects survival and cytokine profile of human Jurkat T lymphocyte exposed to simulated microgravity.
abstract: A growing body of evidence strongly indicates that both simulated and authentic weightlessness exert a broad range of effects on mammalian tissues and cells, including impairment of immune cell function and increased apoptotic death. We previously reported that microgravity-dependent activation of 5-lipoxygenase (5-LOX) might play a central role in the initiation of apoptosis in human T lymphocytes, suggesting that the upregulation of this enzyme might be (at least in part) responsible for immunodepression observed in astronauts during space flights. Herein, we supplement novel information about the molecular mechanisms underlying microgravity-triggered apoptotic cell death and immune system deregulation, demonstrating that under simulated microgravity human Jurkat T cells increase the content of cytosolic DNA fragments and cytochrome c (typical hallmarks of apoptosis) and have an upregulated expression and activity of µ-calpain. These events were paralleled by the unbalance of interleukin- (IL-) 2 and interferon- (INF-) γ, anti- and proapoptotic cytokines, respectively, that seemed to be dependent on the functional interplay between 5-LOX and µ-calpain. Indeed, we report unprecedented evidence that 5-LOX inhibition reduced apoptotic death, restored the initial IL-2/INF-γ ratio, and more importantly reverted µ-calpain activation induced by simulated microgravity.
authors.affiliation: Department of Experimental Medicine & Surgery, Tor Vergata University of Rome, Via Montpellier 1, 00133 Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Gasperi
authors.affiliation: Faculty of Veterinary Medicine, University of Teramo, Piazza A. Moro 45, 64100 Teramo, Italy ; StemTeCh Group, Via Colle dell'Ara, 66100 Chieti, Italy.
authors.forename: Cinzia
authors.identifier: 0000-0002-9759-2449
authors.initials: C
authors.lastname: Rapino
authors.affiliation: Faculty of Bioscience, Technology for Food Agriculture and Environment, University of Teramo, Piazza A. Moro 45, 64100 Teramo, Italy ; European Center for Brain Research (CERC), IRCCS Santa Lucia Foundation, Via del Fosso di Fiorano 64-65, 00143 Rome, Italy.
authors.forename: Natalia
authors.identifier: 0000-0002-1936-6710
authors.initials: N
authors.lastname: Battista
authors.affiliation: Department of Experimental Medicine & Surgery, Tor Vergata University of Rome, Via Montpellier 1, 00133 Rome, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Bari
authors.affiliation: Department of Experimental Medicine & Surgery, Tor Vergata University of Rome, Via Montpellier 1, 00133 Rome, Italy.
authors.forename: Nicolina
authors.initials: N
authors.lastname: Mastrangelo
authors.affiliation: Center of Integrated Research, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy.
authors.forename: Silvia
authors.identifier: 0000-0002-7393-8732
authors.initials: S
authors.lastname: Angeletti
authors.affiliation: Faculty of Bioscience, Technology for Food Agriculture and Environment, University of Teramo, Piazza A. Moro 45, 64100 Teramo, Italy ; European Center for Brain Research (CERC), IRCCS Santa Lucia Foundation, Via del Fosso di Fiorano 64-65, 00143 Rome, Italy.
authors.forename: Enrico
authors.identifier: 0000-0001-7163-9344
authors.initials: E
authors.lastname: Dainese
authors.affiliation: European Center for Brain Research (CERC), IRCCS Santa Lucia Foundation, Via del Fosso di Fiorano 64-65, 00143 Rome, Italy ; Center of Integrated Research, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy.
authors.forename: Mauro
authors.identifier: 0000-0002-3990-2963
authors.initials: M
authors.lastname: Maccarrone
mesh_terms: D017209:Apoptosis; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation; D018474:Weightlessness Simulation
chemical_list: D016207:Cytokines; D001094:Arachidonate 5-Lipoxygenase; D002154:Calpain; C449002:mu-calpain