5-Lipoxygenase-dependent apoptosis of human lymphocytes in the International Space Station: data from the ROALD experiment

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.