title: 5-Lipoxygenase-dependent apoptosis of human lymphocytes in the International Space Station: data from the ROALD experiment.
abstract: The functional adaptation of the immune system to the surrounding environment is also a fundamental issue in space. It has been suggested that a decreased number of lymphocytes might be a cause of immunosuppression, possibly due to the induction of apoptosis. Early activation of 5-lipoxygenase (5-LOX) might play a central role in the initiation of the apoptotic program. The goal of the role of apoptosis in lymphocyte depression (ROALD) experiment, flown on the International Space Station as part of the BIO-4 mission of the European Space Agency, was to ascertain the induction of apoptosis in human lymphocytes under authentic microgravity, and to elucidate the possible involvement of 5-LOX. Our results demonstrate that exposure of human lymphocytes to microgravity for 48 h onboard the ISS remarkably increased apoptotic hallmarks such as DNA fragmentation (∼3-fold compared to ground-based controls) and cleaved-poly (ADP-ribose) polymerase (PARP) protein expression (∼3-fold), as well as mRNA levels of apoptosis-related markers such as p53 (∼3-fold) and calpain (∼4-fold); these changes were paralleled by an early increase of 5-LOX activity (∼2-fold). Our findings provide a molecular background for the immune dysfunction observed in astronauts during space missions, and reveal potential new markers to monitor health status of ISS crew members.
authors.affiliation: Department of Biomedical Sciences, University of Teramo, Piazza A. Moro 45, I-64100 Teramo, Italy.
authors.forename: Natalia
authors.initials: N
authors.lastname: Battista
authors.forename: Maria A
authors.initials: MA
authors.lastname: Meloni
authors.forename: Monica
authors.initials: M
authors.lastname: Bari
authors.forename: Nicolina
authors.initials: N
authors.lastname: Mastrangelo
authors.forename: Grazia
authors.initials: G
authors.lastname: Galleri
authors.forename: Cinzia
authors.initials: C
authors.lastname: Rapino
authors.forename: Enrico
authors.initials: E
authors.lastname: Dainese
authors.forename: Alessandro Finazzi
authors.initials: AF
authors.lastname: Agrò
authors.forename: Proto
authors.initials: P
authors.lastname: Pippia
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccarrone
mesh_terms: D017209:Apoptosis; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D018480:Astronauts; D001483:Base Sequence; D017931:DNA Primers; D006801:Humans; D007391:International Cooperation; D008214:Lymphocytes / Q000166:cytology* / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013026:Space Flight; D014893:Weightlessness
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D001094:Arachidonate 5-Lipoxygenase