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Biomedical subjects

H Michael Tucker

Publications and source records attributed to H Michael Tucker.

3 recordsLinked to original sources
PubMed2002

Urokinase-type plasminogen activator inhibits amyloid-beta neurotoxicity and fibrillogenesis via plasminogen.

Amyloid-beta (Abeta) appears central to Alzheimer's disease (AD), aggregates spontaneously, and is neurotoxic to neurons in vitro. Recently, several groups reported a familial AD locus on chromosome 10. Here, we note that urokinase-type plasminogen activator (uPA) is located within this locus. Previously, we reported that uPA and its functional homolog, tissue-type plasminogen activator, are induced by Abeta treatment of neurons in vitro as well as in a mouse model of Abeta accumulation in vivo. Moreover, the target of plasminogen activators, plasmin, degraded nonaggregated and aggregated Abeta and modulated Abeta toxicity and deposition. Here, we have evaluated the effects of uPA and plasminogen on Abeta fibril formation and neurotoxicity. We report that the combination of uPA and plasminogen, but neither alone, inhibits Abeta toxicity, reduces Abeta deposition in vitro, and inhibits Abeta fibrillogenesis. We interpret these observations as suggesting that uPA represents a possible candidate gene for the chromosome 10 familial AD locus.

Alzheimer Disease↗
PubMed2002

Nerve growth factor-dependent activation of the small GTPase Rin.

The Rit and Rin proteins comprise a distinct and evolutionarily conserved subfamily of Ras-related small GTPases. Although we have defined a role for Rit-mediated signal transduction in the regulation of cell proliferation and transformation, the function of Rin remains largely unknown. Because we demonstrate that Rin is developmentally regulated and expressed in adult neurons, we examined its role in neuronal signaling. In this study, we show that stimulation of PC6 cells with either epidermal growth factor or nerve growth factor (NGF) results in rapid activation of Rin. This activation correlates with the onset of Ras activation, and dominant-negative Ras completely inhibits Rin activation induced by NGF. Further examination of Ras-mediated Rin activation suggests that this process is dependent upon neuronally expressed regulatory factors. Expression of mutationally activated H-Ras fails to activate Rin in non-neuronal cells, but results in potent stimulation of Rin-GTP levels in a variety of neuronal cell lines. Furthermore, although constitutively activated Rin does not induce neurite outgrowth on its own, both NGF-induced and oncogenic Ras-induced neurite outgrowth were inhibited by the expression of dominant-negative Rin. Together, these studies indicate that Rin activation is a direct downstream effect of growth factor-dependent signaling in neuronal cells and suggest that Rin may function to transduce signals within the mature nervous system.

3T3 Cells↗