Our research focuses on oxidative modification of proteins. The resulting covalent modifications are implicated in important physiological and pathological processes. During the current year we continued investigations of the physiological functions of oxidative modification of proteins, the properties and processing of oxidatively modified proteins, and pharmacological and genetic interventions in these processes. In particular, we extended our efforts to produce transgenic and knockout animals with altered methionine sulfoxide reductase activities. Also, for several years we have investigated the mechanism by which the group B streptococcus induces pulmonary hypertension. The group B streptococcus is the most common bacterial infection in the human neonate, and previous investigators provided evidence that the bacterium induces an oxidative stress which might then induce pulmonary hypertension. Utilizing biochemical techniques and bioassays, we showed that the pulmonary hypertension is induced by phospholipids in the bacterial wall. In order to elucidate further the pathways involved, we devoted considerable effort to the construction of a group B streptococcus lacking phosphatidylglycerol synthase, which would prevent synthesis of the hypertension-inducing phospholipids. However, deletion of the synthase proved lethal. We also devoted substantial effort to creation of cell culture models of pulmonary hypertension. We attempted to trigger cultured pulmonary endothelial and/or smooth muscle cells to release thromboxane when exposed to either group B streptococcus or purified phospholipids. These efforts were also unsuccessful, and therefore we have decided not to pursue further studies on the group B streptococcus.
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