Exposure of human lymphocytes and lymphoblastoid cells to simulated microgravity strongly affects energy metabolism and DNA repair

被引:28
作者
Degan, P
Sancandi, M
Zunino, A
Ottaggio, L
Viaggi, S
Cesarone, F
Pippia, P
Galleri, G
Abbondandolo, A
机构
[1] Natl Canc Res Inst, IST, Lab Mutagenesis, Dept Etiol & Epidemiol, I-16132 Genoa, Italy
[2] Univ Genoa, Dept Oncol Biol & Genet, Genoa, Italy
[3] Univ Sassari, Dept Physiol Biochem & Cell Sci, I-07100 Sassari, Italy
关键词
microgravity; energy metabolism; DNA repair; 8-hydroxy-2 '-deoxyguanosine; apoptosis;
D O I
10.1002/jcb.20302
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Exposure of freshly drawn lymphocytes and lymphoblastoid cells (LB and COR3) to simulated microgravity decreased the intracellular ATP concentration to 50%-40% of the value found in normal growth conditions. The decrease was reversible although recovery to normal values occurred only slowly both in lymphocytes and in lymphoblastoid cells. Poly(ADP-ribose) polymerase (PARP) activity was increased indicating that cells exposed to conditions of reduced gravitation experience stress. Exposure to microgravity forces cells into a condition of metabolic quiescence in which they appear to be particularly sensitive to subsequent exposures to a genotoxic agent. Thus, treatment of cells with the strong redox agent potassium bromate under microgravity conditions, indicated an impairment in repair of DNA 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidized derivative of deoxyguanosine. We conclude that gravitational modulation of the kind routinely obtained under laboratory conditions and during spaceflights is a stressful process to which cells appear to be extremely sensitive. These effects may reflect the physiological alterations observed in astronauts and in animals following spaceflights or exposure to conditions of simulated microgravity. (C) 2004 Wiley-Liss, Inc.
引用
收藏
页码:460 / 469
页数:10
相关论文
共 32 条
[1]  
Batkai L, 1999, J Gravit Physiol, V6, pP109
[2]   Poly(APD-ribosyl)ation, a DNA damage-driven protein modification and regulator of genomic instability [J].
Bürkle, A .
CANCER LETTERS, 2001, 163 (01) :1-5
[3]  
Bürkle A, 2000, ANN NY ACAD SCI, V908, P126
[4]   Poly(ADP-ribose) polymerase is affected early by thyroid state during liver regeneration in rats [J].
Cesarone, CF ;
Scarabelli, L ;
Demori, I ;
Balocco, S ;
Fugassa, E .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2000, 279 (06) :G1219-G1225
[5]   THE EFFECT OF HYPOGRAVITY AND HYPERGRAVITY ON CELLS OF THE IMMUNE-SYSTEM [J].
COGOLI, A .
JOURNAL OF LEUKOCYTE BIOLOGY, 1993, 54 (03) :259-268
[6]   CELL SENSITIVITY TO GRAVITY [J].
COGOLI, A ;
TSCHOPP, A ;
FUCHSBISLIN, P .
SCIENCE, 1984, 225 (4658) :228-230
[7]   Effect of spaceflight on human stem cell hematopoiesis: Suppression of erythropoiesis and myelopoiesis [J].
Davis, TA ;
Wiesmann, W ;
Kidwell, W ;
Cannon, T ;
Kerns, L ;
Serke, C ;
Delaplaine, T ;
Pranger, A ;
Lee, KP .
JOURNAL OF LEUKOCYTE BIOLOGY, 1996, 60 (01) :69-76
[8]  
Degan P, 2001, J Gravit Physiol, V8, pP21
[9]   Mechanical culture conditions effect gene expression: gravity-induced changes on the space shuttle [J].
Hammond, TG ;
Benes, E ;
O'Reilly, KC ;
Wolf, DA ;
Linnehan, RM ;
Taher, A ;
Kaysen, JH ;
Allen, PL ;
Goodwin, TJ .
PHYSIOLOGICAL GENOMICS, 2000, 3 (03) :163-173
[10]  
HARLOW F, 1988, ANTIBODIES LAB MANUA