Adaptive response and the influence of ageing: effects of low-dose irradiation on cell growth of cultured glial cells.
OBJECTIVE
To examine the molecular mechanism of radiation adaptive response (RAR) for the growth of cultured glial cells and to investigate the influence of ageing on the response.


METHODS
Glial cells were cultured from young and older rats (1 and 24 months). RAR for the growth of glial cells conditioned with a low dose of X-rays and subsequently exposed to a high dose of X-rays was examined for cell number and BrdU incorporation. Involvement of the subcellular signalling pathway factors in RAR was investigated using their inhibitors, activators, and mutated and knockout glial cells.


RESULTS
RAR was observed in cells cultured from young rats but was not in cells from older animals. The inhibitors of protein kinase C (PKC) and DNA-dependent protein kinase (DNA-PK) or phosphatidylinositol 3-kinase (PI3K) suppressed RAR. The activators of PKC instead of low-dose irradiation also caused RAR. Moreover, glial cells cultured from severe combined immunodeficiency (scid) mice (CB-17 scid) and ataxia-telangiectasia mutated (Atm) knockout mice showed no RAR.


CONCLUSIONS
The results indicated that PKC, ATM, DNAPK and/or PI3K were involved in RAR for growth and BrdU incorporation of cultured glial cells and RAR decreased with ageing.
Miura
Y
Y
Redox Regulation Research Group, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakaecho, Itabashi-ku, Tokyo 173-0015, Japan. miura@centm.center.tmig.or.jp
Abe
K
K
Urano
S
S
Furuse
T
T
Noda
Y
Y
Tatsumi
K
K
Suzuki
S
S
D000367:Age Factors; D000375:Aging; D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002455:Cell Division; D002478:Cells, Cultured; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D004307:Dose-Response Relationship, Radiation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D009457:Neuroglia / Q000166:cytology* / Q000528:radiation effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013997:Time Factors; D014965:X-Rays
D001973:Bromodeoxyuridine; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases