Cell Growth in Microgravity
313
reflection of effect on PKC
per se
.M
i
-
crogravity culture differentially alters the
translocation of individual PKC isoforms
in monocytes and T cells providing a
partial explanation of adverse effects on
T-cell activation. A signiFcant variation in
the intracellular distribution and quan-
tity of PKC according to
g
levels was
also observed in monocytes and periph-
eral blood lymphocytes aboard a Biorack
experiment. These experiments demon-
strate the sensitivity of PKC expression
to gravitational force. There is no clear
demonstration that the PKC changes are
a
direct
consequence
of
variations
in
gravity or an indirect outcome of up-
stream changes as the cell adapts to the
new physical environment. Commensu-
rately, a marked decrease in the expres-
sion
of
the
calcium-independent
PKC
isoforms,
PKC-
δ
and
PKC-
ε
,w
a
sd
e
-
scribed in human lymphocytes exposed
to modeled microgravity culture. ±unc-
tional association in microgravity may be
determined by speciFc blocking of PKC
isoforms expression followed by assess-
ment of T-cell activation and locomotion
both
in
microgravity
and
cell
culture
analog.
Microgravity experiments have been per-
formed on several different mammalian
cells. ±light experiments included HeLa
cervical carcinoma cells, A431 human
epidermoid carcinoma cells, and various
immune cells, including primary isolated
peripheral blood leukocyte populations
and the transformed cell lines of Jurkat
leukemic T cells and monocytic THP-1
cells. While HeLa cells proliferate nor-
mally in microgravity during orbital flight,
other studies revealed responsiveness to
hypergravity. At 10, 35, and 70 G in a
centrifuge, HeLa cell proliferation and
c-
myc
expression were signiFcantly in-
creased. Subsequently,
HeLa displayed
increased
inositol
1,
4,
5-triphosphate
(IP
3
) levels and decreased cAMP levels.
Studies with A431 cells examined the
inducible expression of the transcription
factor c-
fos
. In both clinostat and sounding
rocket studies, the expression of c-
fos
was
suppressed when induced by epidermal
growth factor (EG±) or phorbol ester but
not when induced by a calcium ionophore,
A23187, or by forskolin, an activator of
protein kinase A (PKA). Conversely, the
EG± induced expression of c-
fos
in hy-
pergravity (10 G) was slightly increased.
The studies with A431 cells demonstrate
that alterations in gravity have speciFc
impacts on signal transduction mecha-
nisms. Experiments with ±riend murine
erythroleukemic virus transformed cells,
WI38 human embryonic lung cells, ham-
ster kidney cells, and L8 rat myoblast
cells, demonstrate normal proliferation
and growth in microgravity. Thus, de-
spite changes induced by microgravity,
many cells adapt and proceed with many
functions (i.e. proliferation still intact).
In cultured liver cells, formation of mul-
tidimensional tissue-like spheroids from
primary human liver cells was observed
in modeled microgravity. These spheroids
were composed of hepatocytes and bil-
iary epithelial cells that arranged as bile
duct–like structures along newly formed
vascular sprouts.
Several studies addressed the ability of
proteins and other macromolecules to in-
teract with each other in microgravity.
The binding of (1) EG± to receptors on
rat osteosarcoma cells; (2) EG± to and the
clustering of EG± receptors on A431 cells;
(3) lectin to rhizobia; (4) alpha-fetoprotein
to immobilized monoclonal antibodies;
and (5) Concanavalin A to lymphocytes
were all normal in microgravity. Thus, nor-
mal protein–protein interactions occur in
microgravity.
previous page 987 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 989 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off