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99mTc-Labeled C2a Domain Of Synaptotagmin I As A Target-Specific Molecular Probe For Noninvasive Imaging Of Acute Myocardial Infarction, Ming Zhao, Xiaoguang Zhu, Shundong Ji, Jundong Zhou, Kutlan S. Ozker, Wei Fang, Robert C. Molthen, Robert S. Hellman

Biomedical Engineering Faculty Research and Publications

Abstract: The exposure of phosphatidylserine (PtdS) is a common molecular marker for both apoptosis and necrosis and enables the simultaneous detection of these distinct modes of cell death. Our aim was to develop a radiotracer based on the PtdS-binding activity of the C2A domain of synaptotagmin I and assess ^99mTc-C2A-GST (GST is glutathione S-transferase) using a reperfused acute myocardial infarction (AMI) rat model. Methods: The binding of C2A-GST toward apoptosis and necrosis was validated in vitro. After labeling with ^99mTc via 2-iminothiolane thiolation, radiochemical purity and radiostability were tested. Pharmacokinetics and biodistribution were studied in healthy rats. …

Nanoelectropulse-Driven Membrane Perturbation And Small Molecule Permeabilization, P. Thomas Vernier, Yinghua Sun, Martin A. Gundersen

Bioelectrics Publications

Background
Nanosecond, megavolt-per-meter pulsed electric fields scramble membrane phospholipids, release intracellular calcium, and induce apoptosis. Flow cytometric and fluorescence microscopy evidence has associated phospholipid rearrangement directly with nanoelectropulse exposure and supports the hypothesis that the potential that develops across the lipid bilayer during an electric pulse drives phosphatidylserine (PS) externalization.

Results
In this work we extend observations of cells exposed to electric pulses with 30 ns and 7 ns durations to still narrower pulse widths, and we find that even 3 ns pulses are sufficient to produce responses similar to those reported previously. We show here that in contrast to …

Hmg-Coa Reductase Inhibitors Act Synergistically With Ucn-01 Through Ras Inhibition, Payal Khanna

Theses and Dissertations

The primary objective of this study is to elucidate the mechanism by which the reagent UCN-01 induces apoptosis when administered to leukemia cells along with HmG-CoA reductase inhibitors, mainly the statins. In this study, we demonstrated that exposure of leukemia cell lines to lovastatin (20 uM, 18 hours) and UCN-01 (100 nM, 18 hours) resulted in mitochondria dysfunction, procaspase 3 and 9 cleavage, and PAW degradation along with marked cytochrome C release and apoptosis. Although similar molecular mechanisms have not yet been confirmed in other cancers, our hypothesis holds that enhanced apoptotic effects of UCN-01 are due in part to …