Open Access. Powered by Scholars. Published by Universities.®

Biochemistry, Biophysics, and Structural Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 22 of 22

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Structural Insights Into Dna Replication And Lesion Bypass By Y Family Dna Polymerases, Kevin N. Kirouac Dec 2010

Structural Insights Into Dna Replication And Lesion Bypass By Y Family Dna Polymerases, Kevin N. Kirouac

Electronic Thesis and Dissertation Repository

Y family DNA polymerases are specialized enzymes for replication through sites of DNA damage in the genome. Although the DNA damage bypass activity of these enzymes is important for genome maintenance and integrity, it is also responsible for DNA mutagenesis due to the error-prone nature of the Y family. Understanding how these enzymes select incoming nucleotides during DNA replication will give insight into their role in cancer formation, aging, and evolution. This work attempts to mechanistically explain, primarily through X-ray crystallography and enzymatic activity assays, how Y family polymerases select incoming nucleotides in various DNA replication contexts. Initially, we sought ...


Determination Of Important Ligand Sites For The Interaction With Aminoglycoside Acetyltransferase(3)-Iiib By Nmr, Katherine Jane Woodruff Dec 2010

Determination Of Important Ligand Sites For The Interaction With Aminoglycoside Acetyltransferase(3)-Iiib By Nmr, Katherine Jane Woodruff

Chancellor’s Honors Program Projects

No abstract provided.


Molecular Targets Of Apigenin In Colorectal Cancer Cells: Involvement Of P21, Nag-1 And P53., Yi Zhong, C Krisanapun, Seong-Ho Lee, T Nualsanit, C Sams, P Peungvicha, Seung Baek Nov 2010

Molecular Targets Of Apigenin In Colorectal Cancer Cells: Involvement Of P21, Nag-1 And P53., Yi Zhong, C Krisanapun, Seong-Ho Lee, T Nualsanit, C Sams, P Peungvicha, Seung Baek

Seung J Baek

Persuasive epidemiological and experimental evidence suggests that dietary flavonoids have anti-cancer activity. Since conventional therapeutic and surgical approaches have not been able to fully control the incidence and outcome of most cancer types, including colorectal neoplasia, there is an urgent need to develop alternative approaches for the management of cancer. We sought to develop the best flavonoids for the inhibition of cell growth, and apigenin (flavone) proved the most promising compound in colorectal cancer cell growth arrest. Subsequently, we found that pro-apoptotic proteins (NAG-1 and p53) and cell cycle inhibitor (p21) were induced in the presence of apigenin, and kinase ...


Mcc-555-Induced Nag-1 Expression Is Mediated In Part By Klf4., Maria Cekanova, Seong-Ho Lee, Michael Mcentee, Seung Baek Oct 2010

Mcc-555-Induced Nag-1 Expression Is Mediated In Part By Klf4., Maria Cekanova, Seong-Ho Lee, Michael Mcentee, Seung Baek

Maria Cekanova MS, RNDr, PhD

Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a central role in cell differentiation, metabolism and tumorigenesis. We have investigated the therapeutic properties of 5-[[6-[(2-fluorophenyl)-methoxy]-2-napthalenyl]-methyl]-2,4-thiazolidinedione (MCC-555) a PPARgamma agonist in human colorectal cancer cells. To elucidate the molecular mechanism(s), by which MCC-555 exerts its effects on the human colorectal cancer cells, we have analyzed the expression of two pro-apoptotic proteins, Krüppel-like factor 4 (KLF4) and nonsteroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1). MCC-555-induced expression of the transcription factor, KLF-4 was blocked by a PPARgamma specific antagonist GW9662 in PPARgamma-dependent manner in HCT-116 cells. We ...


Epicatechin Gallate Suppresses Oxidative Stress-Induced Muc5ac Overexpression By Interaction With Epidermal Growth Factor Receptor, Hj Kim, Jh Ryu, Ch Kim, Jw Lim, Uy Moon, Gh Lee, Seung Baek, Jh Yoon Aug 2010

Epicatechin Gallate Suppresses Oxidative Stress-Induced Muc5ac Overexpression By Interaction With Epidermal Growth Factor Receptor, Hj Kim, Jh Ryu, Ch Kim, Jw Lim, Uy Moon, Gh Lee, Seung Baek, Jh Yoon

Seung J Baek

The goal of this study was to investigate the effect of epicatechin gallate (ECG), a component of green tea polyphenols, on the signal pathway for oxidative stress-induced intracellular reactive oxygen species (ROS) generation and MUC5AC overexpression in normal human nasal epithelial (NHNE) cells. Passage-2 NHNE cells were used, and ECG was administered before stimulation with exogenous hydrogen peroxide (H(2)O(2)). MUC5AC gene and protein levels were measured by real-time PCR and dot blot analysis. Western blot analysis and immunocytofluorescence study were performed for detecting the activity of epidermal growth factor receptor (EGFR). Exogenous H(2)O(2) increases ...


Activating Transcription Factor 2 (Atf2) Controls Tolfenamic Acid-Induced Atf3 Expression Via Map Kinase Pathways., Seong-Ho Lee, Jae Hoon Bahn, Nichelle Whitlock, Seung Baek Aug 2010

Activating Transcription Factor 2 (Atf2) Controls Tolfenamic Acid-Induced Atf3 Expression Via Map Kinase Pathways., Seong-Ho Lee, Jae Hoon Bahn, Nichelle Whitlock, Seung Baek

Seung J Baek

Tolfenamic acid (TA) is a non-steroidal anti-inflammatory drug associated with anti-tumorigenic and pro-apoptotic properties in animal and in vitro models of cancer. However, the underlying cellular mechanisms by which TA exerts its effects are only partially understood. Activating transcription factor 3 (ATF3) is a member of the ATF/CREB subfamily of the basic region-leucine zipper family and has been known as a tumor suppressor in human colorectal cancer cells. The present study was performed to observe whether ATF3 mediates TA-induced apoptosis and to elucidate the molecular mechanism of ATF3 transcription induced by TA. TA treatment and ectopic expression of ATF3 ...


Specific, Reversible Cytostatic Protection Of Normal Cells Against Negative Effects Of Chemotherapy, Benjamin B. Mull Aug 2010

Specific, Reversible Cytostatic Protection Of Normal Cells Against Negative Effects Of Chemotherapy, Benjamin B. Mull

UT GSBS Dissertations and Theses (Open Access)

Chemotherapy is a common and effective method to treat many forms of cancer. However, treatment of cancer with chemotherapy has severe side effects which often limit the doses of therapy administered. Because some cancer chemotherapeutics target proliferating cells and tissues, all dividing cells, whether normal or tumor, are affected. Cell culture studies have demonstrated that UCN-01 is able to reversibly and selectively arrest normal dividing cells; tumor cells lines do not undergo this temporary arrest. Following UCN-01 treatment, normal cells displayed a 50-fold increase in IC50 for camptothecin; tumor cells showed no such increased tolerance.

We have examined the response ...


Autonomous Bioluminescent Expression Of The Bacterial Luciferase Gene Cassette (Lux) In A Mammalian Cell Line, Dan Close, Patterson, Ripp, Seung Baek, Sanseverino, Gary Sayler Jul 2010

Autonomous Bioluminescent Expression Of The Bacterial Luciferase Gene Cassette (Lux) In A Mammalian Cell Line, Dan Close, Patterson, Ripp, Seung Baek, Sanseverino, Gary Sayler

Seung J Baek

No abstract provided.


(-)-Epigallocatechin-3-Gallate (Egcg) Post-Transcriptionally And Post-Translationally Suppresses The Cell Proliferative Protein Trop2 In Human Colorectal Cancer Cells., Seung Baek, Mugdha Sukhthankar, Saverio Alberti Jul 2010

(-)-Epigallocatechin-3-Gallate (Egcg) Post-Transcriptionally And Post-Translationally Suppresses The Cell Proliferative Protein Trop2 In Human Colorectal Cancer Cells., Seung Baek, Mugdha Sukhthankar, Saverio Alberti

Seung J Baek

BACKGROUND: TROP-2 is a tumor-promoting molecule that has been found to be overexpressed in many cancer cells, making it a plausible biomarker of carcinogenesis. The main aim of this study was to examine the effect of green tea catechins (namely, (-)-epigallocatechin-3-gallate; EGCG) on TROP-2 expression. MATERIALS AND METHODS: Western blot and RT-PCR were applied to assess TROP2 expression in colorectal cancer cells and tissues. RESULTS: Two different mechanisms were found to operate in diverse cell lines. In SW480 cells, EGCG affected the post-transcriptional processing of the TROP-2 mRNA, as this was quickly and specifically degraded in the presence of EGCG ...


Mcc-555-Induced Nag-1 Expression Is Mediated In Part By Klf4., Maria Cekanova, Seong-Ho Lee, Michael Mcentee, Seung Baek Jul 2010

Mcc-555-Induced Nag-1 Expression Is Mediated In Part By Klf4., Maria Cekanova, Seong-Ho Lee, Michael Mcentee, Seung Baek

Seong-Ho Lee

Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a central role in cell differentiation, metabolism and tumorigenesis. We have investigated the therapeutic properties of 5-[[6-[(2-fluorophenyl)-methoxy]-2-napthalenyl]-methyl]-2,4-thiazolidinedione (MCC-555) a PPARgamma agonist in human colorectal cancer cells. To elucidate the molecular mechanism(s), by which MCC-555 exerts its effects on the human colorectal cancer cells, we have analyzed the expression of two pro-apoptotic proteins, Krüppel-like factor 4 (KLF4) and nonsteroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1). MCC-555-induced expression of the transcription factor, KLF-4 was blocked by a PPARgamma specific antagonist GW9662 in PPARgamma-dependent manner in HCT-116 cells. We ...


Mcc-555-Induced Nag-1 Expression Is Mediated In Part By Klf4., Maria Cekanova, Seong-Ho Lee, Michael Mcentee, Seung Baek Jun 2010

Mcc-555-Induced Nag-1 Expression Is Mediated In Part By Klf4., Maria Cekanova, Seong-Ho Lee, Michael Mcentee, Seung Baek

Seung J Baek

Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a central role in cell differentiation, metabolism and tumorigenesis. We have investigated the therapeutic properties of 5-[[6-[(2-fluorophenyl)-methoxy]-2-napthalenyl]-methyl]-2,4-thiazolidinedione (MCC-555) a PPARgamma agonist in human colorectal cancer cells. To elucidate the molecular mechanism(s), by which MCC-555 exerts its effects on the human colorectal cancer cells, we have analyzed the expression of two pro-apoptotic proteins, Krüppel-like factor 4 (KLF4) and nonsteroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1). MCC-555-induced expression of the transcription factor, KLF-4 was blocked by a PPARgamma specific antagonist GW9662 in PPARgamma-dependent manner in HCT-116 cells. We ...


Poisonous Rangeland Plants In San Luis Obispo County, Sara Litten, Amanda Ou Jun 2010

Poisonous Rangeland Plants In San Luis Obispo County, Sara Litten, Amanda Ou

Animal Science

Poisonous Rangeland Plants in San Luis Obispo County is a comprehensive educational guide to rangeland plants that are toxic to domestic livestock. This guide begins with an exploration of how the biological systems are affected by the poisonous plant toxins. The biochemistry behind these toxins is included in the discussion. Next, reference material for fourteen plants that inhabit San Luis Obispo County is provided. This information includes specific toxins found in poisonous plants, affected animals, symptoms of poisoning, stages of growth, lethal dose, and distribution of the plant in California. This section of the guide is filled with helpful photos ...


Natural Selection On Epas1 (Hif2Α) Associated With Low Hemoglobin Concentration In Tibetan Highlanders, Cynthia M. Beall, Gianpiero L. Cavalleri, Libin Deng, Robert C. Elston, Yang Gao, Jo Knight, Chaohua Li, Jiang Chuan Li, Yu Liang, Mark Mccormack, Hugh E. Montgomery, Hao Pan, Peter A. Robbins, Kevin V. Shianna, Siu Cheung Tam, Ngodup Tsering, Krishna Veeramah, Wei Wang, Puchung Wangdui, Michael E. Weale, Yaomin Xu, Zhe Xu, Ling Yang, M Justin Zaman, Changqing Zeng, Li Zhang, Xianglong Zhang, Pingcuo Zhaxi, Yong Tang Zheng Jun 2010

Natural Selection On Epas1 (Hif2Α) Associated With Low Hemoglobin Concentration In Tibetan Highlanders, Cynthia M. Beall, Gianpiero L. Cavalleri, Libin Deng, Robert C. Elston, Yang Gao, Jo Knight, Chaohua Li, Jiang Chuan Li, Yu Liang, Mark Mccormack, Hugh E. Montgomery, Hao Pan, Peter A. Robbins, Kevin V. Shianna, Siu Cheung Tam, Ngodup Tsering, Krishna Veeramah, Wei Wang, Puchung Wangdui, Michael E. Weale, Yaomin Xu, Zhe Xu, Ling Yang, M Justin Zaman, Changqing Zeng, Li Zhang, Xianglong Zhang, Pingcuo Zhaxi, Yong Tang Zheng

Molecular and Cellular Therapeutics Articles

By impairing both function and survival, the severe reduction in oxygen availability associated with high-altitude environments is likely to act as an agent of natural selection. We employed genomic and candidate gene approaches to search for evidence of such genetic selection. First, a genome-wide allelic differentiation scan (GWADS) comparing indigenous highlanders of the Tibetan Plateau (3200-3500m) with closely related lowland Han revealed a genome-wide significant divergence across eight SNPs located near EPAS1. This gene encodes the transcription factor HIF2α, which stimulates production of red blood cells and thus increases the concentration of hemoglobin in blood. Second, in a separate cohort ...


Effects Of Atmospheric Non-Thermal Plasma On Invasion Of Colorectal Cancer Cells., Seung Baek, Chul-Ho Kim, S Kwon, K Lee, S Jun, Philip Rack May 2010

Effects Of Atmospheric Non-Thermal Plasma On Invasion Of Colorectal Cancer Cells., Seung Baek, Chul-Ho Kim, S Kwon, K Lee, S Jun, Philip Rack

Seung J Baek

No abstract provided.


Xenoestrogen-Specific Mechanisms Of Developmental Reprogramming Correlate With Gene Expression And Tumor Development, Kristen L. Greathouse May 2010

Xenoestrogen-Specific Mechanisms Of Developmental Reprogramming Correlate With Gene Expression And Tumor Development, Kristen L. Greathouse

UT GSBS Dissertations and Theses (Open Access)

Environmental exposures during sensitive windows of development can reprogram normal physiological responses and alter disease susceptibility later in life in a process known as developmental reprogramming. We have shown that neonatal exposure to the xenoestrogen diethylstilbestrol (DES) can developmentally reprogram the reproductive tract in genetically susceptible Eker rats giving rise to complete penetrance of uterine leiomyoma. Based on this, we hypothesized that xenoestrogens, including genistein (GEN) and bisphenol A (BPA), reprogram estrogen-responsive gene expression in the myometrium and promote the development of uterine leiomyoma. We proposed the mechanism that is responsible for the developmental reprogramming of gene expression was through ...


Expression Of The Periplaneta Americana's Α-Adrenergic-Like Octopamine Receptor In The Yeast Saccharomyces Cerevisiae: A High-Throughput Screening System In Search Of Biorational Insecticides, Aaron Donald Gross Jan 2010

Expression Of The Periplaneta Americana's Α-Adrenergic-Like Octopamine Receptor In The Yeast Saccharomyces Cerevisiae: A High-Throughput Screening System In Search Of Biorational Insecticides, Aaron Donald Gross

Graduate Theses and Dissertations

The use of conventional synthetic insecticides is facing increased scrutiny due to environmental and mammalian health concerns along with resistance to target insects. This has led to an investigation of alternative control measures to combat both economically and medically important arthropods. Octopamine, a biogenic amine, has significant physiological functions in invertebrates, including insects, and signals through G-protein-coupled receptors (GPCRs). Co-evolution of plants with insects has led to plants adapting defensive mechanisms to deter herbivore, microbial, or viral attack. This is sometimes accomplished via the production of essential oils that are composed of a variety of compounds, in particular monoterpenoids, sesquiterpenoids ...


Synthesis And Evaluation Of Azetidinone Analogues Of Combretastatin A-4 As Tubulin Targeting Agents, Niamh O'Boyle, Miriam Carr, Lisa M. Greene, Orla Bergin, Seema M. Nathwani, Thomas Mccabe, David G. Lloyd, Daniela M. Zisterer, Mary J. Meegan Jan 2010

Synthesis And Evaluation Of Azetidinone Analogues Of Combretastatin A-4 As Tubulin Targeting Agents, Niamh O'Boyle, Miriam Carr, Lisa M. Greene, Orla Bergin, Seema M. Nathwani, Thomas Mccabe, David G. Lloyd, Daniela M. Zisterer, Mary J. Meegan

Articles

The synthesis and antiproliferative activity of a new series of rigid analogues of combretastatin A-4 are described which contain the 1,4-diaryl-2-azetidinone (β-lactam) ring system in place of the usual ethylene bridge present in the natural combretastatin stilbene products. These novel compounds are also substituted at position 3 of the β-lactam ring with an aryl ring. A number of analogues showed potent nanomolar activity in human MCF-7 and MDA-MB-231 breast cancer cell lines, displayed in vitro inhibition of tubulin polymerization and did not cause significant cytotoxicity in normal murine breast epithelial cells. 4-(4-Methoxyaryl)-substituted compound 32, 4-(3-hydroxy-4-methoxyaryl)-substituted ...


Characterization Of Arsd: An Arsenic Chaperone For The Arsab As(Iii)-Translocating Atpase, Jianbo Yang Jan 2010

Characterization Of Arsd: An Arsenic Chaperone For The Arsab As(Iii)-Translocating Atpase, Jianbo Yang

Wayne State University Dissertations

Arsenic is a metalloid toxicant that is widely distributed throughout the earth's crust and causes a variety of health and environment problems. As an adaptation to arsenic-contaminated environments, organisms have developed resistance systems. In bacteria and archaea various ars operons encode ArsAB ATPases that pump the trivalent metalloids As(III) or Sb(III) out of cells. In these operons, an arsD gene is almost always adjacent to the arsA gene, suggesting a related function. ArsA is the catalytic subunit of the pump that hydrolyzes ATP in the presence of arsenite or antimonite. ArsB is a membrane protein which containing ...


Cell Adhesion Property Affected By Cyclooxygenase And Lipoxygenase: Opto-Electric Approach (With Chang Kyoung Choi, Mugdha Sukhthankar, Chul-Ho Kim, Seong-Ho Lee, Anthony English, Kenneth D. Kihm., Seung Baek Dec 2009

Cell Adhesion Property Affected By Cyclooxygenase And Lipoxygenase: Opto-Electric Approach (With Chang Kyoung Choi, Mugdha Sukhthankar, Chul-Ho Kim, Seong-Ho Lee, Anthony English, Kenneth D. Kihm., Seung Baek

Seung J Baek

Expression of cyclooxygenases (COX) and lipoxygenases (LOX) has been linked to many pathophysiological phenotypes, including cell adhesion. However, many current approaches to measure cellular changes are performed only in a fixed-time point. Since cells dynamically move in conjunction with the cell matrix, there is a pressing need for dynamic or time-dependent methods for the investigation of cell properties. In the presented study, we used stable human colorectal cancer cell lines ectopically expressing COX-1, COX-2, and 15LOX-1, to investigate whether expression of COX-1, COX-2, or 15LOX-1 would affect cell adhesion using our opto-electric methodology. In a fixed-time point experiment, only COX-1- ...


Nsaid-Activated Gene-1 As A Molecular Target For Capsaicin-Induced Apoptosis Through A Novel Molecular Mechanism Involving Gsk3beta, C/Ebpbeta And Atf3, Seung Baek, Seong-Ho Lee, Chutwadee Krisanapun Dec 2009

Nsaid-Activated Gene-1 As A Molecular Target For Capsaicin-Induced Apoptosis Through A Novel Molecular Mechanism Involving Gsk3beta, C/Ebpbeta And Atf3, Seung Baek, Seong-Ho Lee, Chutwadee Krisanapun

Seung J Baek

Capsaicin, a natural product of the Capsicum species of red peppers, is known to induce apoptosis and suppress growth. Non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) is a cytokine associated with pro-apoptotic and antitumorigenic property in colorectal and lung cancer. Our data demonstrate that capsaicin leads to induction of apoptosis and up-regulates NAG-1 gene expression at the transcriptional level. Overexpression of CCAAT/enhancer binding protein beta (C/EBPbeta) caused a significant increase of basal and capsaicin-induced NAG-1 promoter activity. We subsequently identified C/EBPbeta binding sites in the NAG-1 promoter responsible for capsaicin-induced NAG-1 transactivation. Electrophoretic mobility shift assay and chromatin immunoprecipitation ...


A Potential Proliferative Gene, Nudt6, Is Down-Regulated By Green Tea Catechins At The Posttranscriptional Level, Seung Baek, Mugdha Sukthankar, Ck Choi, A English, Js Kim Dec 2009

A Potential Proliferative Gene, Nudt6, Is Down-Regulated By Green Tea Catechins At The Posttranscriptional Level, Seung Baek, Mugdha Sukthankar, Ck Choi, A English, Js Kim

Seung J Baek

The main aims of this study were to elucidate the effect of green tea catechins on Nudix-type motif 6 (NUDT6) suppression and to characterize NUDT6's biological activity. Our microarray data showed that the green tea component epicatechin-3-gallate suppressed NUDT6 expression, and this was confirmed by RT-PCR. Subsequently, the use of different catechins showed that the effect of epigallocatechin-3-gallate (EGCG) was stronger than that of other catechins. At the posttranscriptional level, EGCG decreased the RNA stability of NUDT6, indicating it as a potential mechanism of NUDT6 suppression. Further cloning of the 3' untranslated region of human NUDT6 mRNA resulted in ...


In Vitro Anti-Proliferative Activity Of Alcoholic Stem Extract Of Coscinium Fenestratum In Human Colorectal Cancer Cells, P Rojsanga, M Sukthankar, C Krisanapun, W Gritsanapan, D Lawson, Seung Baek Dec 2009

In Vitro Anti-Proliferative Activity Of Alcoholic Stem Extract Of Coscinium Fenestratum In Human Colorectal Cancer Cells, P Rojsanga, M Sukthankar, C Krisanapun, W Gritsanapan, D Lawson, Seung Baek

Seung J Baek

Coscinium fenestratum (Gaertn.) Colebr. is traditionally used for the treatment of cancer, arthritis and diabetes mellitus. The purpose of this study was to determine the molecular mechanisms by which this plant shows beneficial effects. An 80% ethanolic extract of C. fenestratum (80ET) was separated by its polarity into dichloromethane (DCM) and aqueous fractions (WF), and the anti-proliferative effects of 80ET, DCM and WF were investigated. Berberine, one of the major components of C. fenestratum, was used as a control. The 80ET, DCM, WF and berberine showed anti-proliferative activity as assessed by cell growth assay. Subsequently, the pro-apoptotic proteins NAG-1 and ...