Overexpression of human thioredoxin in transgenic mice controls oxidative stress and life span.

Transgenic (Tg) mice overexpressing human thioredoxin (TRX), a small redox-active protein, were produced to investigate the role of the protein in a variety of stresses. Bone marrow cells from TRX-Tg mice were more resistant to ultraviolet C-induced cytocide compared with those from wild type (WT) C57BL/6 mice. TRX-Tg mice exhibited extended median and maximum life spans compared with WT mice. Telomerase activity in spleen tissues in TRX-Tg mice was higher than that in WT mice. These results suggest that overexpression of TRX results in resistance against oxidative stress and a possible extension of life span without apparent abnormality in mammals.

[1]  D. Bowen,et al.  Oxidative Stress and the Myelodysplastic Syndromes , 2003, International journal of hematology.

[2]  M. Chung,et al.  Oxidative status in senescence-accelerated mice. , 1996, The journals of gerontology. Series A, Biological sciences and medical sciences.

[3]  K. Yoshida,et al.  Calorie restriction reduces the incidence of myeloid leukemia induced by a single whole-body radiation in C3H/He mice. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Y. Yamaoka,et al.  Adult T cell leukemia-derived factor/human thioredoxin protects endothelial F-2 cell injury caused by activated neutrophils or hydrogen peroxide. , 1994, Immunology letters.

[5]  S. Osborne,et al.  Thioredoxin-mediated redox control of the transcription factor Sp1 and regulation of the thioredoxin gene promoter. , 2003, Gene.

[6]  R. Weindruch,et al.  The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. , 1986, The Journal of nutrition.

[7]  Sandy Chang,et al.  Longevity, Stress Response, and Cancer in Aging Telomerase-Deficient Mice , 1999, Cell.

[8]  B. Yu,et al.  Aging and oxidative stress: modulation by dietary restriction. , 1996, Free radical biology & medicine.

[9]  R. S. Sohal,et al.  Hydrogen peroxide production by liver mitochondria in different species , 1990, Mechanisms of Ageing and Development.

[10]  H. Masutani,et al.  Redox regulation by thioredoxin in cardiovascular diseases. , 2003, Antioxidants & redox signaling.

[11]  F. Ishikawa,et al.  A novel quantitative 'stretch PCR assay', that detects a dramatic increase in telomerase activity during the progression of myeloid leukemias. , 1996, Oncogene.

[12]  Béla Ágai,et al.  CONDENSED 1,3,5-TRIAZEPINES - V THE SYNTHESIS OF PYRAZOLO [1,5-a] [1,3,5]-BENZOTRIAZEPINES , 1983 .

[13]  H. Nakamura,et al.  Redox regulation of cellular activation. , 1997, Annual review of immunology.

[14]  Pier Paolo Pandolfi,et al.  The p66shc adaptor protein controls oxidative stress response and life span in mammals , 1999, Nature.

[15]  M. Blasco,et al.  Disease states associated with telomerase deficiency appear earlier in mice with short telomeres , 1999, The EMBO journal.

[16]  H. Masutani,et al.  The role of thioredoxin in the aging process: involvement of oxidative stress. , 2003, Antioxidants & redox signaling.

[17]  T. Hagen Oxidative stress, redox imbalance, and the aging process. , 2003, Antioxidants & redox signaling.

[18]  H. Masutani,et al.  Hemin-induced Activation of the Thioredoxin Gene by Nrf2 , 2001, The Journal of Biological Chemistry.

[19]  J. Yodoi,et al.  Reactive oxygen-reducing and protein-refolding activities of adult T cell leukemia-derived factor/human thioredoxin. , 1992, Biochemical and biophysical research communications.

[20]  K. Arai,et al.  ATL‐derived factor (ADF), an IL‐2 receptor/Tac inducer homologous to thioredoxin; possible involvement of dithiol‐reduction in the IL‐2 receptor induction. , 1989, The EMBO journal.

[21]  T. Zglinicki Telomeres: Influencing the Rate of Aging , 1998, Annals of the New York Academy of Sciences.

[22]  K. Arai,et al.  Hematopoietic and lymphopoietic responses in human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor transgenic mice injected with human GM-CSF. , 1997, Blood.

[23]  K. Nozaki,et al.  Overexpression of thioredoxin in transgenic mice attenuates focal ischemic brain damage. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[24]  R. S. Sohal,et al.  Relationship between antioxidant defenses and longevity in different mammalian species , 1990, Mechanisms of Ageing and Development.