RRC ID 43699
Author Nishizawa H, Handayaningsih AE, Iguchi G, Cho Y, Takahashi M, Yamamoto M, Suda K, Kasahara K, Hakuno F, Yamanouchi K, Nishihara M, Seino S, Takahashi S, Takahashi Y.
Title Enhanced oxidative stress in GH-transgenic rat and acromegaly in humans.
Journal Growth Horm IGF Res
Abstract BACKGROUND:Excessive oxidative stress plays a causal role in various diseases such as diabetes, hypertension, atherosclerosis, and heart failure. Acromegaly is a pathological condition associated with excess growth hormone (GH) and insulin-like growth factor-I (IGF-I) and a high prevalence of diabetes, hypertension, atherosclerosis, and heart failure; resulting in premature death. We hypothesized that these conditions may be associated with increased oxidative stress.
OBJECTIVE AND METHODS:We explored the oxidative stress levels in the serum and tissues of GH-transgenic rats as an animal model for acromegaly. We also measured the oxidative stress levels in the serum of patients with acromegaly and age-, sex-, and BMI-matched control subjects. We examined the effects of GH and IGF-I on reactive oxygen species (ROS) production in C2C12 myocytes.
RESULTS:The levels of an oxidative stress marker, serum thiobarbituric acid reactive substances (TBARS) were increased in the GH-transgenic rats. Further, tissue oxidative stress damage was enhanced in the cardiomyocytes and vascular smooth muscle cells in the aorta of the GH-transgenic rats. In addition, serum TBARS levels and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were increased in acromegaly in humans. IGF-I but not GH induced ROS production in C2C12 myocytes in vitro.
CONCLUSIONS:These data indicate that the increased levels of IGF-I are associated with enhanced oxidative stress in rats and humans. In addition, increased ROS may play an important role in the complications and premature death in acromegaly.
Volume 22(2)
Pages 64-8
Published 2012-4
DOI 10.1016/j.ghir.2012.02.001
PII S1096-6374(12)00015-9
PMID 22370764
MeSH Acromegaly / metabolism* Animals Animals, Genetically Modified Dose-Response Relationship, Drug Female Growth Hormone / genetics Growth Hormone / metabolism* Humans Insulin-Like Growth Factor I / metabolism Male Mice Muscle Cells / cytology Oxidative Stress* Oxygen / chemistry Prevalence Rats Reactive Oxygen Species
IF 2.167
Times Cited 23
Human and Animal Cells