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Publication : Antioxidant enzymes, free-radical damage, and response to paraquat in liver and kidney of long-living growth hormone receptor/binding protein gene-disrupted mice.

First Author  Hauck SJ Year  2002
Journal  Horm Metab Res Volume  34
Issue  9 Pages  481-6
PubMed ID  12384824 Mgi Jnum  J:80522
Mgi Id  MGI:2446007 Doi  10.1055/s-2002-34787
Citation  Hauck SJ, et al. (2002) Antioxidant enzymes, free-radical damage, and response to paraquat in liver and kidney of long-living growth hormone receptor/binding protein gene-disrupted mice. Horm Metab Res 34(9):481-6
abstractText  Numerous studies have shown that the lifespan can be extended by caloric restriction or by altering the growth hormone (GH)-insulin-like growth factor 1 signaling pathway. Both of these manipulations produce physiological alterations, such as increased insulin sensitivity, and reduced glucose levels and body size. However, it is difficult to evaluate whether these are merely correlates of delayed aging or whether they have a direct causal effect on lifespan. One parameter that has been demonstrated to have causal, positive effects on longevity in invertebrates is improved antioxidant defenses. We measured activities of antioxidant enzymes Cu/Zn superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) and quantified free-radical damage by lipid peroxidation (LP) and protein oxidation (PO) measurements in liver and kidney tissues, and evaluated the response to paraquat-induced oxygen toxicity in the long-living GH receptor/binding protein gene knockout (GHR-KO) mouse. We found that in the kidney, SOD was lower and GPx was higher in GHR-KO mice, and LP was higher in female GHR-KO mice only. In the liver, female GHR-KO mice had lower GPx, while male GHR-KO mice had lower CAT and higher LP. GHR-KO males were also more susceptible to paraquat toxicity compared to females or normal males. We conclude that in long-living GHR-KO mice, GH-resistance does not confer longevity by improved free-radical scavenging in the liver and kidney, suggesting that greater free-radical defenses in other tissues, or altered glucose metabolism may have a more central role in extending the lifespan of these animals.
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