Abstract
The physiological roles of the protease inhibitor SERPINB3 (SB3) are still largely unknown. The study was addressed to assess the biological effects of this serpin in vivo using a SB3 transgenic mouse model. Two colonies of mice (123 transgenic for SB3 and 148 C57BL/6J controls) have been studied. Transgenic (TG) mice showed longer survival than controls and the difference was more remarkable in males than in females (18.5% vs 12.7% life span increase). In TG mice decreased IL-6 in serum and lower p66shc in the liver were observed. In addition, TG males showed higher expression of mTOR in the liver. Liver histology showed age-dependent increase of steatosis and decrease of glycogen storage in both groups and none of the animals developed neoplastic lesions. In conclusion, the gain in life span observed in SB3-transgenic mice could be determined by multiple mechanisms, including the decrease of circulating IL-6 and the modulation of ageing genes in the liver.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aging
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Animals
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / metabolism*
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Fatty Liver / pathology
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Female
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Glycogen / metabolism
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Hep G2 Cells
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Humans
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Interleukin-6 / blood
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Liver / metabolism
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Liver / pathology
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Longevity / genetics*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Protease Inhibitors / chemistry
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Protease Inhibitors / metabolism
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RNA, Messenger / metabolism
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Serpins / genetics
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Serpins / metabolism*
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Shc Signaling Adaptor Proteins / genetics
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Shc Signaling Adaptor Proteins / metabolism
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Src Homology 2 Domain-Containing, Transforming Protein 1
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TOR Serine-Threonine Kinases / genetics
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TOR Serine-Threonine Kinases / metabolism
Substances
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Antigens, Neoplasm
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Interleukin-6
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Protease Inhibitors
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RNA, Messenger
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Serpins
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Shc Signaling Adaptor Proteins
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Shc1 protein, mouse
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Src Homology 2 Domain-Containing, Transforming Protein 1
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squamous cell carcinoma-related antigen
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Glycogen
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TOR Serine-Threonine Kinases