Two specific goals were addressed for this dissertation. First to investigate and identify the mechanistic profile of ketoconazole (KT)-induced hepatotoxicity by utilizing in vivo and in vitro approaches determining the mechanism of action for the hepatotoxicity incurred. To date, there has not been a mechanistic determination of the hepatotoxicity associated...
Rat selenoprotein W (SeW) promoter activity was investigated using different concentrations of cadmium, copper, and zinc. Two fragments (404bp and 1265bp) of the SeW promoter, containing a single metal response element (MRE), were ligated into the multiple cloning site of a pGL3-Basic reporter plasmid. The constructs were transfected into cultured...
We compared a kinetic method (KM) and a colorimetric method (CM) for
measuring erythrocyte aspartate aminotransferase (EAST) activity. Twenty-three
healthy college students including 7 men and 16 women, aged from 22 to 40 years,
participated in this study. Vitamin B-6 status was assessed by EAST activity
coefficient (EAST-AC), the ratio...
Dithiocarbamates are widely used agricultural pesticides, industrial chemicals and
effluent additives. DTCs and their related compounds have historical and current
relevance in clinical and experimental medicine. DTC developmental toxicity is well
established, but poorly understood. Dithiocarbamates according to the U.S. EPA have a
mechanism of action involving, "the inhibition of...
Studies using the pluripotent embryonic carcinoma cell line, P19, as a retinoic acid (RA)-responsive model system have been instrumental towards our understanding of the RA-dependent signaling pathways in development and homeostasis. Grp1-associated scaffold protein (GRASP; also known as Tamalin) was first identified by our group, as a gene robustly induced...
This thesis describes an investigation of the molecular basis of the substrate specificity and catalytic mechanism of a unique pseudoglycosyltransferase (PsGT) enzyme, VldE. PsGTs are a newly discovered group of glycosyltransferase (GT)-like proteins that catalyze the transfer of a pseudosugar to an acceptor molecule via a C-N bond formation. This...
Two novel and highly related C₂H₂ zinc finger proteins (CTIP1/BCL11A/EVI9 and CTIP2/BCL11B/Rit1) have been implicated in COUP-TF signaling, etiology of myeloid and lymphoid malignancies, and hematopoietic cell development. However, the precise cellular function(s) and the contribution of these proteins to neoplastic processes and hematopoietic cell development remain unknown. The goal...