title: Modest inhibition of the growth hormone axis does not affect mitochondrial reactive oxygen species generation or redox state, unlike calorie restriction.
abstract: OBJECTIVE
  Modest inhibition of the growth hormone (GH) axis by overexpression of the antisense GH gene in male Wistar rats reduced food intake and body weight, and lengthened the lifespan, even if fed ad libitum (AL). These findings were comparable with those induced by 30% calorie restriction (CR) in wild-type (WT) rats, suggesting importance of the GH signal pathway in the effect of CR. The present study evaluated the effects of GH inhibition and CR on mitochondrial oxidative stress and redox state in the liver.
  
  
  METHODS
  Transgenic and WT rats were fed AL or 30% CR diets from 6weeks of age. Liver tissues were collected at 6 and 24months of age. The mitochondria fraction was prepared from liver tissue homogenates. The total reactive oxygen species (ROS) generation, the protein levels of glutathione (GSH) and oxidized GSH (GSSG), and the superoxide dismutase 2 activity were measured.
  
  
  RESULTS
  The results revealed that CR, but not modest inhibition of GH, decreased mitochondrial ROS generation and increased the mitochondrial GSH redox potential.
  
  
  CONCLUSIONS
  The present study suggests that CR affects mitochondrial function and redox state through a pathway distinct from GH signaling.
authors.affiliation: Department of Investigative Pathology, Unit of Basic Medical Science Department of Biochemistry and Molecular Biology in Diseases, Atomic Bomb Disease Institute, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hayashida
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Komatsu
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Henmi
authors.forename: Kurumi
authors.initials: K
authors.lastname: Yanagihara-Ota
authors.forename: Ae-Ra
authors.initials: AR
authors.lastname: Kim
authors.forename: Takuya
authors.initials: T
authors.lastname: Chiba
authors.forename: Shinji
authors.initials: S
authors.lastname: Goto
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
authors.forename: Isao
authors.initials: I
authors.lastname: Shimokawa
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D031204:Caloric Restriction; D005978:Glutathione / Q000378:metabolism; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D005978:Glutathione; D013006:Growth Hormone; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2