[A model system for the assessment of the stability of eukaryotic genes and expressed proteins in extended space flight].
Evidence was obtained that the changed gravity, tension profiles of the magnetic fields inside the orbital station and other spaceflight factors (SFF) substantially influence the cell genome and synthesis of recombinant proteins. The authors proposed a technique of fixation of possible alterations in genes and expressed recombinant proteins in strains-producers of human alpha-interferon: HuIFN-alpha 2b, HuIFN-alpha 8a, HuIFN-alpha 10a, and HuIFN-alpha 14a. Spaceflight factors were simulated by way of gamma-irradiation at 10 Gy and 50 Gy by a cobalt unit, and centrifugation of samples at 10 g and 50 g. Cultivation of the strains-producers during the SFF simulation yielded HuIFN-alpha proteins with altered functional characteristics. Following exposure to simulated SFF, strains-producers expressed HuIFN-alpha that preserved a high titre of antiviral activity (AVA) but suppressed the antiproliferative activity (APA) inferring some structural/functional shifts in the HuIFN-alpha molecule due to, presumably, mutations in the active center responsible for APA. Determination of species specificity of the HuIFN-alpha recombinant proteins following exposure to SFF revealed dissociation of cross-AVA in homologous and heterologous cell cultures which can be also attributed to the structural/functional shifts in the HuIFN-alpha molecule. These changes can be localized in the receptor cluster of molecule or consequent to modification of the center defining HuIFN-alpha species specificity. The proposed simulation system allows fixation of shifts in the HuIFN-alpha structural/functional characteristics and investigations of the stability of eucaryotic genes in long-term space flights.
Kalinin
Iu T
IuT
Timofeev
I V
IV
Paletskaia
T F
TF
Perminova
N G
NG
Gileva
I P
IP
Shcherbakov
G Ia
GIa
D002465:Cell Movement / Q000502:physiology; D004926:Escherichia coli / Q000235:genetics; D005057:Eukaryotic Cells / Q000502:physiology*; D005818:Genetic Engineering; D006801:Humans; D018471:Hypergravity; D018472:Hypogravity; D007369:Interferon Inducers; D016898:Interferon-alpha / Q000235:genetics*; D011994:Recombinant Proteins / Q000235:genetics*; D013026:Space Flight; D013997:Time Factors
D007369:Interferon Inducers; D016898:Interferon-alpha; D011994:Recombinant Proteins