A5003153494- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Liver physiology and pathology
- Organ Transplantation Techniques and Outcomes
- Folate and B Vitamins Research
- Pancreatic function and diabetes
- Neuroscience and Neuropharmacology Research
- Liver Disease Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Metabolomics and Mass Spectrometry Studies
- Wnt/β-catenin signaling in development and cancer
- Anesthesia and Neurotoxicity Research
- Cardiac Ischemia and Reperfusion
- Cancer-related gene regulation
- Peroxisome Proliferator-Activated Receptors
- Protein Kinase Regulation and GTPase Signaling
- Amino Acid Enzymes and Metabolism
- Liver Disease and Transplantation
- Cancer therapeutics and mechanisms
- Neurological diseases and metabolism
- Memory and Neural Mechanisms
- Adenosine and Purinergic Signaling
- Bioactive Compounds and Antitumor Agents
- Tryptophan and brain disorders
- Drug Transport and Resistance Mechanisms
David H. Murdock Research Institute
2018-2021
University of North Carolina at Chapel Hill
2004-2020
Medical University of South Carolina
2009-2010
University of Pittsburgh
2001-2003
Duke Medical Center
1991
National Institute of Environmental Health Sciences
1988
The wnt/β–catenin pathway is important during embryogenesis and carcinogenesis. β–Catenin interaction with E–cadherin has been shown to be crucial in cell–cell adhesion. We report novel findings the wnt rat liver regeneration after 70% partial hepatectomy using Western blot analyses, immunoprecipitation studies, immunofluorescence. found wnt–1 β–catenin proteins predominantly localized hepatocytes. Immediately following hepatectomy, we observed an initial increase protein first 5 minutes its...
Hepatocyte growth factor/scatter factor (HGF/SF) is a pluripotent capable of acting as motogen, morphogen, and mitogen. Originally, HGF/SF was found blood-borne mitogen for hepatocytes has since been determined to be very important in liver repair. Previous studies have established that must proteolytically cleaved elicit its effects. After injury by toxins such carbon tetrachloride or after surgical resection, partial hepatectomy (PHX), concentrations increase the blood. The aims this study...
Graft failure after liver transplantation may involve mitochondrial dysfunction. We examined whether prevention of injury would improve graft function. Orthotopic rat was performed 18 hours' cold storage in University Wisconsin solution and treatment with vehicle, minocycline, tetracycline, or N -methyl-4-isoleucine cyclosporin (NIM811) explants recipients. Serum alanine aminotransferase (ALT), necrosis, apoptosis were assessed 6 hours implantation. Mitochondrial polarization cell viability...
We investigated the effects of nitric oxide (NO) on hepatocellular killing after simulated ischemia/reperfusion and characterized signaling factors triggering cytoprotection by NO. Cultured rat hepatocytes were incubated in anoxic Krebs-Ringer-HEPES buffer at pH 6.2 for 4 hours reoxygenated 7.4 2 hours. During reoxygenation, some exposed to combinations NO donors (S-nitroso-N-acetylpenicillamine [SNAP] others), a cGMP analogue (8-bromoguanosine-3,5-cGMP [8-Br-cGMP]), cGMP-dependent protein...
Adaphostin is a dihydroquinone derivative that undergoing extensive preclinical testing as potential anticancer drug. Previous studies have suggested the generation of reactive oxygen species (ROS) plays critical role in cytotoxicity this agent. In study, we investigated source these ROS. Consistent with known chemical properties dihydroquinones, adaphostin simultaneously underwent oxidation to corresponding quinone and generated ROS under aqueous conditions. Interestingly, however, was not...
Abstract Background Mitochondrial folate enzyme ALDH1L2 (aldehyde dehydrogenase 1 family member L2) converts 10-formyltetrahydrofolate to tetrahydrofolate and CO 2 simultaneously producing NADPH. We have recently reported that the lack of due compound heterozygous mutations was associated with neuro-ichthyotic syndrome in a male patient. Here, we address role cellular metabolism highlight mechanism by which regulates lipid oxidation. Methods generated Aldh1l2 knockout (KO) mouse model,...
ALDH1L1 (10-formyltetrahydrofolate dehydrogenase), an enzyme of folate metabolism highly expressed in liver, metabolizes 10-formyltetrahydrofolate to produce tetrahydrofolate (THF). This reaction might have a regulatory function towards reduced pools, de novo purine biosynthesis, and the flux folate-bound methyl groups. To understand role cellular metabolism, Aldh1l1-/- mice were generated using ES cell clone (C57BL/6N background) from KOMP repository. Though viable did not apparent...
NO and cGMP administered at reperfusion after ischaemia prevent injury to hepatocytes mediated by the MPT (mitochondrial permeability transition). To characterize further mechanism of protection, ability hepatic cytosol in combination with cyclic nucleotides delay onset calcium-induced was evaluated isolated rat liver mitochondria. Liver plus or cAMP dose-dependently inhibited MPT, required ATP hydrolysis for inhibition did not inhibit mitochondrial calcium uptake. Specific peptide...
Neuro-ichthyotic syndromes are a group of rare genetic diseases mainly associated with perturbations in lipid metabolism, intracellular vesicle trafficking, or glycoprotein synthesis. Here, we report patient neuro-ichthyotic syndrome deleterious mutations the ALDH1L2 (aldehyde dehydrogenase 1 family member L2) gene encoding for mitochondrial 10-formyltetrahydrofolate dehydrogenase. Using fibroblast culture established from ALDH1L2-deficient patient, demonstrated that enzyme loss impaired...
ALDH1L1 is a folate-metabolizing enzyme abundant in liver and several other tissues. In human cancers cell lines derived from malignant tumors, the gene commonly silenced through promoter methylation. It was suggested that limits proliferation capacity of thus functions as putative tumor suppressor. contrast to cancer cells, mouse NIH3T3 AML12 do express protein. present study, we show levels these fluctuate throughout cycle. During S-phase, markedly down regulated at protein level. As...
Cytosolic 10-formyltetrahydrofolate dehydrogenase (ALDH1L1) is commonly downregulated in human cancers through promoter methylation. We proposed that ALDH1L1 loss promotes malignant tumor growth. Here, we investigated the effect of Aldh1l1 mouse knockout (Aldh1l1−/−) on hepatocellular carcinoma using a chemical carcinogenesis model. Fifteen-day-old male mice and their wild-type littermate controls (Aldh1l1+/+) were injected intraperitoneally with 20 μg/g body weight DEN (diethylnitrosamine)....
Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional cytokine that involved in many normal as well pathological conditions. HGF/NK1, splice variant of HGF/SF, has been reported to have either antagonistic or agonistic effects with regard c-Met signaling depending on the cell type. In these experiments, we determined HGF/NK1 potent mitogen for rat hepatocytes culture. Furthermore, found coagulation Xa (fXa) capable cleaving and single chain HGF/SF (scHGF/SF). The products...
Many oxygen mass-transfer modeling studies have been performed for various bioartificial liver (BAL) encapsulation types; yet, to our knowledge, there is no experimental study that directly and noninvasively measures viability metabolism as a function of time concentration. We report the effect concentration on in fluidized-bed NMR-compatible BAL using vivo ³¹P ¹³C NMR spectroscopy, respectively, by monitoring nucleotide triphosphate (NTP) ¹³C-labeled nutrient metabolites, respectively....