The underlying premise of this work is that inhibition of proteolysis observed during aging results in an inhibition of cell proliferation responses, as exemplified by reduced immune function, liver regeneration, and wound-healing. In this proposal, it is hypothesized that inhibition of cysteine proteinases by thiostatin results in impairment in the cell's ability to respond to mitogenic stimuli. To test this, it is proposed to identify: (1) the site(s) within the cell cycle that are affected by thiostatin overexpression, and (2) the molecular mechanisms responsible for inhibition of the MAP kinase pathway of signal transduction in thiostatin-producing cells.
| Donoso, Veronica; Gomez, Christian R; Orriantia, Miguel Angel et al. (2008) The release of sympathetic neurotransmitters is impaired in aged rats after an inflammatory stimulus: a possible link between cytokine production and sympathetic transmission. Mech Ageing Dev 129:728-34 |
| Perez, Viviana; Leiva-Salcedo, Elias; Acuna-Castillo, Claudio et al. (2006) T-kininogen induces endothelial cell proliferation. Mech Ageing Dev 127:282-9 |
| Gomez, Christian R; Acuna-Castillo, Claudio; Nishimura, Sumiyo et al. (2006) Serum from aged F344 rats conditions the activation of young macrophages. Mech Ageing Dev 127:257-63 |
| Acuna-Castillo, Claudio; Leiva-Salcedo, Elias; Gomez, Christian R et al. (2006) T-kininogen: a biomarker of aging in Fisher 344 rats with possible implications for the immune response. J Gerontol A Biol Sci Med Sci 61:641-9 |
| Acuna-Castillo, Claudio; Aravena, Mauricio; Leiva-Salcedo, Elias et al. (2005) T-kininogen, a cystatin-like molecule, inhibits ERK-dependent lymphocyte proliferation. Mech Ageing Dev 126:1284-91 |
| Perez, Viviana; Velarde, Victoria; Acuna-Castillo, Claudio et al. (2005) Increased kinin levels and decreased responsiveness to kinins during aging. J Gerontol A Biol Sci Med Sci 60:984-90 |
| Aravena, M; Perez, C; Perez, V et al. (2005) T-kininogen can either induce or inhibit proliferation in Balb/c 3T3 fibroblasts, depending on the route of administration. Mech Ageing Dev 126:399-406 |
| Li, Min; Torres, Claudio; Acuna-Castillo, Claudio et al. (2002) Defect in ERK2 and p54(JNK) activation in aging mouse splenocytes. J Gerontol A Biol Sci Med Sci 57:B41-7 |
| Torres, C; Li, M; Walter, R et al. (2001) T-kininogen inhibits fibroblast proliferation in the G(1) phase of the cell cycle. Exp Cell Res 269:171-9 |
| Torres, C; Li, M; Walter, R et al. (2000) Modulation of the ERK pathway of signal transduction by cysteine proteinase inhibitors. J Cell Biochem 80:23-Nov |
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