Pharmacology Commons^™

Structural Basis For Chloroperoxidase Catalyzed Enantioselective Epoxidations And Mechanisms Of Selected Anticancer Drug Induced Apoptosis, Yongjian Guo

FIU Electronic Theses and Dissertations

Chloroperoxidase (CPO), a member of the heme peroxidase family, has diverse catalytic activities toward a broad range of substrates. In addition to catalyzing halogenation reactions involved in the biosynthesis of halogen-containing compounds, CPO also catalyzes reactions typical of traditional heme peroxidases, catalases, and cytochrome P450 enzymes. Despite the powerful and versatile catalytic activity of CPO, its applications have been thwarted by the difficulty in regenerating the active enzyme and substrate (peroxide) induced protein inactivation. To overcome these shorting comings of the protein, we investigate the fabrication and characterization of chloroperoxidase (CPO) and glucose oxidase (GOx) on the surface of MGO. …

Investigation Of Riluzole’S Synaptic Protection Mechanism Through Hsf1-Bdnf Axis, Yi Zhang

Theses and Dissertations (ETD)

The FDA-approved amyotrophic lateral sclerosis (ALS) drug Riluzole has great potential in treating Alzheimer’s disease (AD) based on promising animal data as well as its known action on modulating synaptic transmission. However, its detailed mechanism of action is not fully understood. Here, we proposed work aiming to address this aspect via focus- ing on the Heat Shock Factor 1 (HSF1)-dependent mechanisms. We found that Riluzole could increase HSF1 and BDNF (Brain-Derived Neurotrophic Factor) expression both at transcriptional and translational levels. CA1 (Cornu Ammonia, the first region in the hip- pocampal circuit), is its main target. We also demonstrated a protective …

Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara

Biological Sciences Theses and Dissertations

Multidrug resistance (MDR) is a major cause of chemotherapy failure. Overexpression of ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are two well-studied drug transporters which are associated with MDR. These two transporters also act as a major functional unit of the blood brain barrier to protect the brain from xenobiotics and toxins. Lack of clinically approved P-gp and BCRP inhibitors renders chemotherapy treatments of many MDR cancers ineffective and obstructs drug uptake into the brain.

Using computational methods, we have identified new compounds that inhibit P-gp (Brewer et al., Mol. Pharmacol. 2014). Several of …

Elucidation Of The Molecular Mechanisms Of Electrically-Induced Cardioprotection, Anne Elizabeth Roessler

Dissertations

Cardiovascular disease is the leading cause of death worldwide. A myocardial infarction (MI), commonly known as a heart attack, is a major event in cardiovascular disease characterized by reduced blood flow to the heart. The ischemia and reperfusion (I/R) injury associated with an MI results in a region of dead tissue in the heart called an infarct, the size of which influences patient prognosis. In the 1980s, it was discovered that short, non-lethal episodes of I/R, termed ischemic preconditioning (IPC), can protect the heart against a subsequent MI. Ischemic preconditioning demonstrated the phenomenon of endogenous cardioprotection. Cardioprotection has great potential …

A Mechanistic Study Of The Teratogenic Potential Of 4-O-Methylhonokiol (Mh) On Japanese Medaka (Oryzias Latipes), Santu Kumar Singha

Electronic Theses and Dissertations

An additional goal of this project was to characterize the Wnt/β-catenin signaling pathway to unravel the adverse potential of MH on the cardiovascular system (CVS). Our study suggested that MH-mediated cardiovascular injury may be caused due to upregulation of some major components of the Wnt/β-catenin pathway through expression of excessive pro-inflammatory mediators. Moreover MH decreased expression of ErbB3 and NRG-2 suggesting impaired cardiac structure. MH exposure caused a slow heartbeat blood occlusion absence of blood circulation decreased hatching efficiency and increased mortality in medaka embryos in a concentration- and time-dependent manner. MH might cause blood vessel occlusion by increasing the …

Implementing Mass Spectrometry For The Structural And Compositional Analysis Of Proteins, Mohammad Riaz

Electronic Theses and Dissertations

Lectins are sugar-binding proteins that perform various biological functions such as cellular recognition attachments etc. Pulses the dried edible seeds of certain plants are great sources of lectins and a proteomics approach directed at lectins identification would bring substantial improvement in the lectin identification process. Lectins from nine different plant species were analyzed through SDS-PAGE and proteomics analysis. After LC-MS/MS analysis proteins were identified with protein database searches using Uniprot. Functionally uncharacterized proteins were identified with database searches were annotated with the Pfam and NCBI-CCD databases. In-vitro pharmacological screening will be carried out to assess the pharmacological effects of these …