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Full-Text Articles in Life Sciences

Role Of Trp Channels In Mediating The Calcium Signaling Response Of Brain Endothelial Cells To Mechanical Stretch, Jonathan Berrout May 2012

Role Of Trp Channels In Mediating The Calcium Signaling Response Of Brain Endothelial Cells To Mechanical Stretch, Jonathan Berrout

Dissertations & Theses (Open Access)

Traumatic brain injury (TBI) often results in disruption of the blood brain barrier (BBB), which is an integral component to maintaining the central nervous system homeostasis. Recently cytosolic calcium levels ([Ca2+]i), observed to elevate following TBI, have been shown to influence endothelial barrier integrity. However, the mechanism by which TBI-induced calcium signaling alters the endothelial barrier remains unknown. In the present study, an in vitro BBB model was utilized to address this issue. Exposure of cells to biaxial mechanical stretch, in the range expected for TBI, resulted in a rapid cytosolic calcium increase. Modulation of intracellular and extracellular …


Targeting Α4 Integrin Containing Complexes In Multiple Myeloma Using Peptidomimetics, Michael Foster Emmons Jan 2012

Targeting Α4 Integrin Containing Complexes In Multiple Myeloma Using Peptidomimetics, Michael Foster Emmons

USF Tampa Graduate Theses and Dissertations

In our previous work we demonstrated that the integrin antagonist, HYD1, induced necrotic cell death in myeloma cell lines in vitro and in vivo as a single agent. In order to further delineate biomarkers of response to HYD1 we developed an isogenic drug resistant variant named H929-60. We show that the acquisition of resistance towards HYD1 correlates with reduced expression of the cleaved α4 integrin subunit and beta 1 integrin. Moreover, we demonstrate that HYD1 interacts with α4 integrin in myeloma cells. Consistent with reduced VLA-4 expression, the resistant variant showed ablated functional binding to fibronectin, VCAM-1 and the bone …