Biomedical subjects

Melanie A Smith

Publications and source records attributed to Melanie A Smith.

2 recordsLinked to original sources

PubMed2005

Transforming growth factor-beta is activated by plasmin and inhibits smooth muscle cell death in human saphenous vein.

BACKGROUND: The effect of activation of endogenous transforming growth factor-beta (TGF-beta) on smooth muscle cell apoptosis was assessed in human saphenous vein. METHODS: Segments of human saphenous vein, obtained at the time of bypass graft surgery, were cultured for 14 days. During this time, smooth muscle cells accumulated in the intima as a result of proliferation and migration, partly counterbalanced by apoptotic cell death. RESULTS: Addition of exogenous TGF-beta(1) had no effect on smooth muscle cell proliferation or apoptosis. However, antibody neutralization of endogenous TGF-beta(1) caused significant increases in smooth muscle cell death in the media and intima without any change in proliferation. A plasmin inhibitor (alpha-N-acetyl-L-lysine methyl ester), a specific urokinase-type plasminogen activator (uPA) inhibitor (amiloride) and an anti-catalytic anti-uPA antibody all caused decreases in the tissue content of active TGF-beta and increases in smooth muscle cell death in the media and intima. CONCLUSIONS: These data suggest that the amount of TGF-beta in human saphenous vein is sufficient, when in the active form, to protect smooth muscle cells against apoptosis. Adding exogenous TGF-beta(1) has no beneficial effect, but decreasing the amount of active TGF-beta causes smooth muscle cells to undergo apoptosis. Plasmin, generated by uPA, appears to be an important activator of endogenous latent TGF-beta.

Amiloride↗

PubMed2003

Interactions between centromere complexes in Saccharomyces cerevisiae.

We have purified two new complexes from Saccharomyces cerevisiae, one containing the centromere component Mtw1p together with Nnf1p, Nsl1p, and Dsn1p, which we call the Mtw1p complex, and the other containing Spc105p and Ydr532p, which we call the Spc105p complex. Further purifications using Dsn1p tagged with protein A show, in addition to the other components of the Mtw1p complex, the two components of the Spc105p complex and the four components of the previously described Ndc80p complex, suggesting that all three complexes are closely associated. Fluorescence microscopy and immunoelectron microscopy show that Nnf1p, Nsl1p, Dsn1p, Spc105p, and Ydr532p all localize to the nuclear side of the spindle pole body and along short spindles. Chromatin immunoprecipitation assays show that all five proteins are associated with centromere DNA. Homologues of Nsl1p and Spc105p in Schizosaccharomyces pombe also localize to the centromere. Temperature-sensitive mutations of Nsl1p, Dsn1p, and Spc105p all cause defects in chromosome segregation. Synthetic-lethal interactions are found between temperature-sensitive mutations in proteins from all three complexes, in agreement with their close physical association. These results show an increasingly complex structure for the S. cerevisiae centromere and a probable conservation of structure between parts of the centromeres of S. cerevisiae and S. pombe.

Amino Acid Sequence↗