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Metallothionein levels and multimeric forms in delayed and premature aging mouse models
Author(s) -
Swinscoe John C.,
BrownBorg Holly M.,
Bartke Andrzej,
Carlson Edward C.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1086
Subject(s) - medicine , oxidative stress , genetically modified mouse , metallothionein , endocrinology , transgene , biology , mutant , knockout mouse , glutathione , ageing , western blot , gene , receptor , genetics , biochemistry , enzyme
The concept that growth hormone (GH) can regulate lifespan and resistance to oxidative stress in mammals is plausible because delayed aging is a notable characteristic of GH‐deficient (Ames dwarf) and GH‐resistant mutant and gene knock‐out mice, while overexpression of endogenous GH (GH‐transgenic mice) is associated with a variably shortened lifespan. Our hypothesis is that the cumulative effect of oxidative damage accelerates aging while antioxidant defense mechanisms affords protection. In the current study, we quantified metallothionein (MT) in PEPCK‐GH‐Tg mice (GH‐transgenic model, 40–50% reduction in lifespan) and in GH‐R/BP gene‐disrupted mice (GH receptor knock‐out model, 40–60% increase in lifespan) using competitive ELISA. MT (ug/mg protein) is elevated in GH‐R knock‐out 210 day old mice compared with age‐matched controls (kidney: 0.234±0.046 vs 0.173, ±0.04; heart: 0.72±0.18 vs 0.54±0.12; liver: 0.172±0.057 vs 0.148±0.045). Surprisingly, MT levels in corresponding 150 or 233 day hemizygous GH‐transgenic mouse tissues were similar to sibling controls, and markedly lower (>50%) than the other models. Western blot data indicate that metal‐bridged hexamers predominate in the kidney and tetramers predominate in the heart and liver in all three mouse models. Thus, while it is known that MT is elevated in the Ames dwarf and GH‐R/BP knock‐out mice, lower MT levels may not provide adequate protection against oxidative damage emanating from excessive circulating levels of GH in the GH‐Tg mouse.