TY - JOUR
T1 - Acute stress response modified by modest inhibition of growth hormone axis
T2 - A potential machinery of the anti-aging effect of calorie restriction
AU - Komatsu, Toshimitsu
AU - Trindade, Lucas S.
AU - Chiba, Takuya
AU - Hayashi, Hiroko
AU - Henmi, Tomoko
AU - Ushiroda, Yoko
AU - Mori, Ryoichi
AU - Shimokawa, Isao
N1 - Funding Information:
We are grateful to Yutaka Araki, Yuko Moriyama, Rieko Tahara, and the staff at the Laboratory Animal Center for Biomedical Research, Center for Frontier Sciences at Nagasaki University, for their excellent technical support. This work was supported by Grants-in-Aid for Science Research from the Japan Society for the Promotion of Science (Nos. 15390128 and 16790226 ).
Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/3
Y1 - 2011/3
N2 - Calorie restriction (CR) may exert antiaging effects by inhibiting the growth hormone (GH)/IGF-1 axis. The present study investigated the effect of modest inhibition of GH signaling on stress response and compared it with the effect of CR. Heterozygous (tg/-) rats of a transgenic strain of male rats, whose GH signaling was inhibited by overexpression of the anti-sense GH gene, and wild-type (WT) rats were used. Rats were fed ad libitum (AL) or 30% CR diets from 6 weeks of age. At 6 months of age, rats were killed between 0 and 8. h after lipopolysaccharide (LPS) injection to evaluate the acute phase stress response. tg/- rats had less tissue injury, indicated by blood aspartate aminotransferase (AST) concentrations, than WT rats. Successive waves of incremental plasma TNF-α, IL-6, and interferon (IFN)-γ levels were also attenuated in tg/- rats. Activation of NF-κB, a redox-sensitive transcription factor, was slightly diminished in tg/- rats, whereas the AP-1 activity was increased. Similar trends were also observed in the CR groups as compared to the AL groups. The present results suggest an involvement of the GH/IGF-1 axis in the effect of CR for stress response, even if CR does not act solely through the GH axis.
AB - Calorie restriction (CR) may exert antiaging effects by inhibiting the growth hormone (GH)/IGF-1 axis. The present study investigated the effect of modest inhibition of GH signaling on stress response and compared it with the effect of CR. Heterozygous (tg/-) rats of a transgenic strain of male rats, whose GH signaling was inhibited by overexpression of the anti-sense GH gene, and wild-type (WT) rats were used. Rats were fed ad libitum (AL) or 30% CR diets from 6 weeks of age. At 6 months of age, rats were killed between 0 and 8. h after lipopolysaccharide (LPS) injection to evaluate the acute phase stress response. tg/- rats had less tissue injury, indicated by blood aspartate aminotransferase (AST) concentrations, than WT rats. Successive waves of incremental plasma TNF-α, IL-6, and interferon (IFN)-γ levels were also attenuated in tg/- rats. Activation of NF-κB, a redox-sensitive transcription factor, was slightly diminished in tg/- rats, whereas the AP-1 activity was increased. Similar trends were also observed in the CR groups as compared to the AL groups. The present results suggest an involvement of the GH/IGF-1 axis in the effect of CR for stress response, even if CR does not act solely through the GH axis.
KW - Calorie restriction
KW - Endotoxin
KW - Growth hormone
KW - Inflammation
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U2 - 10.1016/j.mad.2011.01.002
DO - 10.1016/j.mad.2011.01.002
M3 - Article
C2 - 21291903
AN - SCOPUS:79952740766
SN - 0047-6374
VL - 132
SP - 103
EP - 109
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
IS - 3
ER -