Biology Commons^™

Microrna-34a Regulates Brain-Derived Neurotrophic Factorin An Intracerebral Hemorrhage Model, Jin Hee Kim, Jae-Sun Choi

Turkish Journal of Biology

Intracerebral hemorrhages (ICHs) are devastating neurological events frequently resulting in a serious negative prognosis. The exact physiological and disease processes involved in ICHs are complex, but are thought to involve microRNAs (miRNAs), 22 nucleotide small noncoding RNAs that control a variety of normal physiological and disease processes. In this study, we show that a miRNA, miR-34a, regulates BDNF in a model of ICH injury. In particular, we assessed the impact of AM34a, an inhibitor of miR-34a, on the toxicity of thrombin-induced apoptosis and on BDNF-mediated signaling. We investigated the increased expression of miR-34a after an ICH-induced thrombin toxicity injury using …

Tumor Necrosis Factor-Alpha Induced Caspase-3 Activation-Related Inos Gene Expression In Adp-Activated Platelets, Özge Çevi̇k, Zelal Adigüzel, Ahmet Tarik Baykal, Azi̇ze Şener

Turkish Journal of Biology

Platelets are sensitive cells and are easily activated by different stimulants in the circulation system. It is known that tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine and plays a role in inflammation. The role of TNF-α in the apoptotic process in blood platelets is unknown. In order to study the formation of apoptosis in platelets after incubation with TNF-α and/or ADP, several biomarkers were chosen: phosphatidylserine (PS) exposure and P-selectin binding; cGMP, Cyt-c, and Ca2+ levels and NOS activation; and gene and protein expression of caspase-3 and iNOS. Platelets were incubated with 100 pg/mL TNF-α and/or 50 mM iNOS …

Mutagenic Analysis Of Sh3 Binding Site In The Avian Chb6 Alloantigen, Rohini Bhattacharya

College of Science and Health Theses and Dissertations

To effectively eliminate the variety of pathogens that an individual may encounter in their lifetime, the immune system has evolved to recognize many different antigens. Within adaptive immunity there are also safe guards where the self-reactive or defective cells are eliminated (1). The removal of such cells is by apoptosis, which is a form of cell suicide characterized by an orderly breakdown of the cell to limit the leakage of cytoplasmic components that could cause inflammation. Apoptosis can be initiated by signaling through specific cell surface molecules and is carried out by downstream mediators. While several model systems of apoptosis …

Role Of Endoplasmic Reticulum Resident Proteins In Mediation Of Intrinsic Programmed Cell Death (Apoptosis), Surya Pramila Kilaparty

Theses and Dissertations

Inositol polyphosphates (InsPs) are signaling molecules that regulate various cellular processes including apoptosis. Among enzymes that metabolize InsPs, Multiple Inositol Polyphosphate Phosphatase1 (Minpp1) is the only enzyme located in the endoplasmic reticulum (ER). It dephosphorylates more phosphorylated InsPs to less phosphorylated InsPs in vitro. Changes in cellular InsPs are known to regulate apoptosis. Minpp1 is a member of the histidine acid phosphatase family of proteins with functional resemblance to phytases found in lower organisms. Its physiological function in higher animals is not clear. Besides its role in dephosphorylating InsPs, it has been shown to have mutase activity. This enzyme is …

The Resolution Phase Of Nk Cell Proliferation And Ifn Production Following Viral Infection Are Highly Regulated Processes., Leslie Abigail Fogel

Arts & Sciences Graduate Student Theses and Dissertations

In response to MCMV infection, NK cells undergo three distinct phases of proliferation: the non-specific phase mediated by pro-proliferative cytokines; the specific phase mediated by recognition of an MCMV-encoded protein by an NK cell activating receptor, Ly49H; and the resolution phase, whose mechanism is unknown. MCMV infection of RAG mice, which lack all adaptive immune cells, results in prolonged proliferation of NK cells despite similar viral titers compared to wildtype mice. Interestingly, there are different kinetics for Ly49H+ and Ly49H- NK cells. We have identified several additional markers that may distinguish NK cells that have been specifically activated through their …

Rac1 And Ire1 Are Required To Prevent Early Loss Of Intestinal Homeostasis In Drosophila Melanogaster, Mauricio M. Ortega

Dissertations, Masters Theses, Capstones, and Culminating Projects

No abstract available

Apoptotic And Necrotizing Mechanisms Of Recombinant Panton-Valentine Leukocidin In Thp1 Monocytes., Heriberto Deleon Iii

Theses and Dissertations

The Panton-Valentine Leukocidin (PVL) is a highly specialized bacterial exotoxin produced by Staphylococcus aureus. The increased degree of invasiveness of community associated methicillin resistant Staphylococcus aureus (CAMRSA) has been attributed to the relatively high rates of PVL produced by the pathogen, thus increasing pathogenicity and virulence. The increased rates of PVL encoding CAMRSA infections have been correlated with increased rates of necrotizing fasciitis, invasive osteomyelitis and invasive necrotizing pneumococcal infections. Previous research as revealed that PVL has the ability to induce apoptosis at low concentration (5nM-10nM) and necrosis (50-100nM) at high concentrations, with little detail on the mechanism of initiation. …

Mir494 Reduces Renal Cancer Cell Survival Coinciding With Increased Lipid Droplets And Mitochondrial Changes, Punashi Dutta, Edward Haller, Arielle Sharp, Meera Nanjundan

Molecular Biosciences Faculty Publications

Background: miRNAs can regulate cellular survival in various cancer cell types. Recent evidence implicates the formation of lipid droplets as a hallmark event during apoptotic cell death response. It is presently unknown whether MIR494, located at 14q32 which is deleted in renal cancers, reduces cell survival in renal cancer cells and if this process is accompanied by changes in the number of lipid droplets.

Methods: 769-P renal carcinoma cells were utilized for this study. Control or MIR494 mimic was expressed in these cells following which cell viability (via crystal violet) and apoptotic cell numbers (via Annexin V/PI staining) were …

Evaluation Of Apoptotic Cell Death Mechanisms Induced By Hypericin-Mediated Photodynamic Therapy In Colon Cancer Cells, Aysun Kiliç Süloğlu, Eli̇f Karacaoğlu, Güldeni̇z Selmanoğlu, Hayri̇ye Akel, İbrahi̇m Çağatay Karaaslan

Turkish Journal of Biology

Hypericin (HYP)-mediated photodynamic therapy (PDT) is a new alternative treatment strategy for colon cancer inducing various cell-death pathways. Apoptotic cell death is the desired cellular fate in cancer cells. Therefore, we investigated the apoptotic pathways by determining apoptosis-related proteins (survivin, caspase-3, caspase-9, Bcl-2, and Bax) at the mRNA level using real-time polymerase chain reaction (qPCR), and the percentage of survivin was determined by survivin ELISA in HT-29 and Caco-2 colon cancer cell lines. The downregulation of survivin was significant 16 h after PDT for both cells, while caspase-3 upregulation was apparent 24 h after PDT. Caspase-9 and caspase-3 upregulations were …

Cytotoxicity And Antiviral Activity Of Palladium(Ii) And Platinum(Ii) Complexes With 2-(Diphenylphosphino)Benzaldehyde 1-Adamantoylhydrazone, Vera Simic, Stoimir Kolarevic, Ilija Brceski, Dejan Jeremic, Branka Vukovic-Gacic

Turkish Journal of Biology

Metal coordination compounds have an important role in the development of novel drugs. Using the resazurin microtitration assay we assessed the cytotoxicity and antiviral activity of the ligand 2-(diphenylphosphino)benzaldehyde 1-adamantoylhydrazone and its Pd(II) and Pt(II) complexes. Cytotoxicity was tested in A549 human lung adenocarcinoma epithelial cells. We observed that the ligand displayed a more pronounced cytotoxic activity than the platinum-based drug, carboplatin. Morphological evaluation of A549 cells treated with the ligand by acridine orange and ethidium bromide double staining revealed the presence of signs of apoptosis. Antiviral activity against poliovirus type 1 was assessed by examination of the cytopathic effect …

Stains Induce Apoptosis And Autophagy In Primary And Transformed Mast Cells, Patrick A. Paez

Theses and Dissertations

Statin drugs are widely employed in the clinic to reduce serum low density lipoproteins (LDLs) in patients with hypocholesteremia. In addition to their cholesterol-lowering effects through HMG CoA reductase antagonism, isoprenyl lipids necessary for membrane anchorage and signaling of small G-proteins are abrogated. We previously found that statins suppress mast cell activation in murine and human cells, suggesting these drugs might be useful in treating allergic disease. While mast cell function is critical to allergic inflammation, mast cell hyperplasia and survival also impact these diseases, and were not studied in our previous work. In this study, we describe Fluvastatin-mediated apoptosis …

Altered Activation Of Protein Kinase Pkr And Enhanced Apoptosis In Dystonia Cells Carrying A Mutation In Pkr Activator Protein Pact, Lauren S. Vaughn, D. Cristopher Bragg, Nutan Sharma, Sarah Camargos, Francisco Cardoso, Rekha C. Patel

Faculty Publications

PACT is a stress-modulated activator of the interferon-induced double-stranded RNA-activated protein kinase (PKR). Stress-induced phosphorylation of PACT is essential for PACT's association with PKR leading to PKR activation. PKR activation leads to phosphorylation of translation initiation factor eIF2α inhibition of protein synthesis and apoptosis.Arecessively inherited form of early-onset dystonia DYT16 has been recently identified to arise due to a homozygous missense mutation P222L in PACT. To examine if the mutant P222L protein alters the stress-response pathway, we examined the ability of mutant P222L to interact with and activate PKR. Our results indicate that the substitution mutant P222L activates PKR more …

Loss Of Mitochondrial Dna Causes Decreased Cell Viability, Alan M. Herrera

Theses and Dissertations - UTB/UTPA

Mitochondria are an organellar network involved in cellular bioenergetics and apoptosis, and dynamically balance their organization between fusion and fission events. Mitochondrial DNA (mtDNA) and nuclear DNA combine to encode polypeptides for the complexes of oxidative phosphorylation (OXPHOS) in the mitochondrial inner membrane, which generate a transmembrane potential (ΔΨm) to synthesize ATP. Loss of ΔΨm causes mitochondrial fission, which appears to be associated with the progression of apoptosis, a critical cell death mechanism that allows tissue homeostasis, developmental sculpturing, and the removal of unwanted cells. Using cultured human cell models of decreased ΔΨm (both genetic mtDNA-depleted ρ 0 and pharmacological …

One Fish, Two Fish, Red Fish, Blue Fish: The Analysis Of The Specter Cell Cycle Mutant In Zebrafish, Tetiana Petrachkova

Masters Theses

Cell division is controlled by genes that regulate the cell cycle. Here we show that the zebrafish specter (spr) mutant is mutation in the cyclin B1 gene, a gene necessary for the G2 to M transition of the cell cycle.

The spr mutation mapped to the cyclin B1 gene. Sequencing showed a transition (C139→T) that caused a nonsense mutation in exon 2 of the cyclin B1 gene. In situ hybridization of cyclin B1 revealed that the mRNA is absent in the mutant embryo by gastrulation. We found that the earliest visible mutant phenotype was a darkening of the head caused …

Chronic Inflammation As A Result Of Hepatitis C Virus Infection: A Review Of The Literature, Samantha L. Lane

DePaul Discoveries

Approximately 170 million people are infected with Hepatitis C virus (HCV) worldwide^5,6. It is estimated that roughly 80% of those infected suffer from persistent infection with the virus; this persistence of infection is progressive, and over time can lead to fibrosis, cirrhosis, and hepatocellular carcinoma⁷. Chronic inflammation and apoptotic deregulation are both hallmarks of chronic HCV infection, and many molecular pathways are initiated in both the innate and adaptive immune responses during infection with this viral pathogen. The aim of this review was to survey some of the major molecular mechanisms responsible for the induction of …

Transcriptional Regulation By Dax-1 In Pluripotent And Differentiated Cells, Alexandra C. Maramba

Master's Theses

DAX-1, an orphan nuclear hormone receptor, acts mainly as a repressor through transcriptional protein complexes. Its unique structure and specific expression raises questions as to what its precise interactions are and how it mediates its repressive function. While it is known to play a role in sexual development and adrenal insufficiency, expression in certain types of cancer suggests additional functions and interactions. Knock in of DAX-1 into a low-DAX-1 expressing cancer cell line has been previously observed to increase apoptosis, while, inversely, down in a high-DAX-1 expressing cancer cell line shows a decrease in apoptosis. Target genes that belong to …

Histone Deacetylase 6 (Hdac6) Promotes The Pro-Survival Activity Of 14-3-3Ζ Via Deacetylation Of Lysines Within The 14-3-3Ζ Binding Pocket, Jeffrey B. Mortenson, Lisa N. Heppler, Courtney J. Banks, Vajira K. Weerasekara, Matthew D. Whited, Stephen R. Piccolo, William E. Johnson, J. Will Thompson, Joshua L. Andersen

Faculty Publications

The phospho-binding protein 14-3-3ζ acts as a signaling hub controlling a network of interacting partners and oncogenic pathways. We show here that lysines within the 14-3-3ζ binding pocket and protein-protein interface can be modified by acetylation. The positive charge on two of these lysines, Lys49 and Lys120, is critical for coordinating 14-3-3ζ-phosphoprotein interactions. Through screening, we identified HDAC6 as the Lys49/Lys120 deacetylase. Inhibition of HDAC6 blocks 14-3-3ζ interactions with two well described interacting partners, Bad and AS160, which triggers their dephosphorylation at Ser112 and Thr642, respectively. Expression of an acetylation-refractory K49R/K120R mutant of 14-3-3ζ rescues both the HDAC6 inhibitor-induced loss …

Rest Regulatory Circuit Controls Distinct Oncogenic Properties Of Glioblastoma Stem Cells Through Specific Micrornas, Anantha L Marisetty

Dissertations and Theses (Open Access)

Glioblastoma Multiforme (GBM) is the most common and aggressive primary malignant brain tumor in adults. With an average survival of only 12-16 months the prognosis for GBM patients remains dismal, with less than 5% of patients surviving 5 years. New mechanism-based approaches are necessary for the management of patients with GBM. Many GBM tumors are believed to be caused by self-renewing, glioblastoma-derived stem-like cells (GSCs). These GSCs are resistant to chemo- and radiation therapies, and are believed to be responsible for tumor recurrence. In a recent paper from our lab we have shown that REST, RE1-silencing transcription factor, regulates oncogenic …

Exploring The Antibacterial, Antioxidant, And Anticancerproperties Of Lichen Metabolites, Gajendra Shrestha

Theses and Dissertations

Natural products have been a significant source of new drugs, especially in treating cancer, infectious diseases, hypertension, and neurological disorders. Although many natural metabolites have been screened and yielded pharmaceutically important drugs, many potential sources of natural product drug therapies still need to be investigated, including lichens. Lichens are symbiotic systems consisting of a filamentous fungus and a photosynthetic partner (an eukaryotic alga and/or cyanobacterium). Lichens produce an impressive variety of unique secondary compounds and have been used as ingredients in folk medicines for centuries. Demonstrated biological roles based on lichen chemistry include: antibiotics, anti-proliferative, antioxidants, anti-HIV, anti-cancer, immunomodulation, and …

Apoptotic Effect Of Cordycepin On A549 Human Lung Cancer Cell Line, Hardeep Singh Tuli, Gaurav Kumar, Sardul Singh Sandhu, Anil Kumar Sharma, Dharmbir Kashyap

Turkish Journal of Biology

Cordycepin, an active ingredient in the insect fungus Cordyceps militaris, is in a category of compounds that exhibit significant therapeutic activity. The aim of the present study was to investigate the effect of cordycepin on cell proliferation, apoptosis, and cell cycle in A549 human lung cancer cells. MTT assay was used to evaluate the cytotoxic effect of cordycepin on A549 cell growth. Apoptotic effect was observed using cell morphology, DAPI staining, and DNA fragmentation studies. Flow cytometry (FCM) analysis was used to analyze cell cycle status after cordycepin treatment. Furthermore, apoptosis was assayed using annexin V-Alexa Fluor 488. Results of …

Histone Deacetylase Inhibitory Activity Of Hydroxycapsaicin, A Synthetic Derivative Of Capsaicin, And Its Cytotoxic Effects Against Human Colon Cancer Cell Lines, Thanaset Senawong, Paweena Wongphakham, Thussanee Saiwichai, Chanokbhorn Phaosiri, Pakit Kumboonma

Turkish Journal of Biology

Capsaicin possesses cytotoxic/anticancer activity and shares some common structural features, including a benzene ring and a long hydrophobic carbon tail, with the histone deacetylase (HDAC) inhibitors trichostatin A and suberoylanilide hydroxamic acid. The aims of this study were to investigate HDAC inhibitory and cytotoxic activities of a synthetic derivative of capsaicin, hydroxycapsaicin (6-hydroxy-N-(4-hydroxy-3-methoxybenzyl)-8-methylnonenamide), in colon cancer cell lines. Hydroxycapsaicin inhibited HDAC activity in vitro (IC50 = 72 µM) much more effectively than the prototype capsaicin (IC50 > 13.1 mM) and also exhibited HDAC inhibitory activity in human cells (HeLa cells). MTT assay demonstrated that hydroxycapsaicin was less toxic than capsaicin against …

A Protective Role Of Autophagy In A Drosophila Model Of Friedreich's Ataxia (Frda), Luan Wang

Wayne State University Dissertations

Friedreich’s ataxia (FRDA) is an inherited autosomal recessive neurodegenerative disease. It affects 1 in every 50,000 people in central Europe and North America. FRDA is caused by deficiency of Frataxin, an essential mitochondrial iron chaperone protein, and the associated oxidative stress damages. Autophagy, a housekeeping process responsible for the bulk degradation and turnover of long half-life proteins and organelles, is featured by the formation of double-membrane vacuoles and lysosomal degradation. Previous researches indicate that Danon’s disease, the inherited neural disorder disease that shares similar symptoms with FRDA, is due to the malfunction of autophagy. Based on this, we raise the …

Rna Aptamers For Molecular Chaperones Hsp27 And Hsp90, Sathishkumar Kumar Munusamy

Legacy Theses & Dissertations (2009 - 2024)

Hsp90 and Hsp27 are members of the heat shock protein family of chaperones that perform multiple roles in cellular maintenance through protein folding and inhibition of apoptosis. They are abundantly expressed in cells and are over-expressed during conditions of stress. Hsp90 requires ATP for its chaperone function while Hsp27 self-associates into higher order oligomers enclosing its substrate. Their ability to interact with other proteins or with themselves lies at the heart of their mechanisms. The specific consequences of each of their interactions on global cellular health have not yet been fully discovered. The sheer diversity of proteins that interact with …

Inhibitory Effects Of Salicylic Acid On A549 Human Lung Adenocarcinoma Cell Viability, Djanan Vejselova, Hati̇ce Mehtap Kutlu

Turkish Journal of Biology

Antiinflammatory drugs, such as salicylic acid and its metabolite acetylsalicylic acid, have been singled out as apoptosis-inducing agents with antitumoral activity. In addition, they reduce the risk of some cancers via an unclear mechanism. In this study, we have investigated the apoptotic, cytotoxic, and growth-inhibiting effects of salicylic acid on A549, the human lung adenocarcinoma, alveolar epithelial cells. Cytotoxicity was tested using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) colorimetric assay. We observed the ultrastructural and morphological changes in A549 cells by using transmission electron microscopy (TEM) and confocal microscopy. Cell viability was decreased by the optimal concentration (IC50) of 6.0 mM salicylic …

The Effects Of Topical Melatonin On Oxidative Stress, Apoptosis Signals,And P53 Protein Expression During Cutaneous Wound Healing, Azi̇ze Şener, Özge Çevi̇k, Özge Doğan, Nazli Gül Altindi̇ş, Hali̇l Aksoy, Betül Okuyan

Turkish Journal of Biology

Elimination of reactive oxygen species (ROS) can be an important strategy to improve healing of wounds. ROS have an effect on proliferation and cell survival signaling, which results in alteration of apoptotic pathways in cells. Melatonin has antioxidant properties on skin wounds. In our study, we investigated the effects of topical melatonin (3%, w/w) on apoptosis and p53 protein expression together with parameters of oxidative stress in a cutaneous excision wound model. Bcl-2 protein levels in wound tissue at the end of days 3, 7, and 14 were significantly increased, while caspase-3 activity and p53 protein expression in wound tissue …

Systems Biology Approach To Understanding The Control Of Glucose Metabolism In Healthy And Apoptotic Neurons, Hoda Gebril

Electronic Theses and Dissertations

Apoptosis plays a crucial role in sculpting the developing central nervous system (CNS) but can, under certain conditions, contribute to neurodegeneration in the mature CNS. Metabolic disturbances have long been associated with apoptosis-inducing agents, however, the mechanism underlying such changes remains controversial. In this study, our hypotheses was that decreased ATP turnover may bring about other metabolic changes in apoptotic neurons. Accordingly, change in metabolic reactions other than ATP turnover may not be important in the study of apoptotic mechanism. In a living cell, metabolic reactions are highly connected and thus are highly sensitive to kinetic change in one or …

Cross-Talk Between The Tumor Suppressors Par-4 And P53, Tripti Shrestha Bhattarai

Theses and Dissertations--Toxicology and Cancer Biology

This work describes the fascinating interplay between two tumor suppressors Prostate apoptosis response-4 (Par-4) and p53. The guardian of the genome, p53, is frequently mutated in human cancers, and may contribute to therapeutic resistance. However, p53 is intact and functional in normal tissues, and we observed that specific activation of p53 in normal fibroblasts could induce apoptosis selectively in p53-deficient cancer cells. This paracrine apoptotic effect was executed by Par-4 secreted in response to p53 activation. Accordingly, activation of p53 in wild-type mice, but not in p53^-/- or Par-4^-/- mice, caused systemic elevation of Par-4 that induced apoptosis …

In Vitro Antiproliferative/Cytotoxic Activity Of 2,3'-Biindole Against Various Cancer Cell Lines, Sali̇h Ökten, Ramazan Erenler, Tuğba Kul Köprülü, Şaban Teki̇n

Turkish Journal of Biology

2,3'-Biindole (2) was synthesized via bromination of indole (1) with molecular bromine and underwent simultaneous dimerization. Antiproliferative and cytotoxic activity of 2 was investigated in vitro on C6 (rat brain tumor), HeLa (human cervix carcinoma), and HT29 (human colon carcinoma) cells lines by using BrdU cell proliferation ELISA and lactate dehydrogenase (LDH) assays. In contrast to 5-fluorouracil (5-FU), 2,3'-biindole (2) significantly inhibited proliferation of HeLa and HT29 cell lines. According to LDH assay, the cytotoxicity of compound 2 was low on HT29 cell lines and high on HeLa and C6 cell lines. Moreover, 2 did not cause any DNA laddering …

Endogenous Heat Shock Protein Groel Of A. Actinomycetemcomitans Preferentially Targets Primary Human Cd8+ T Cells, Meli̇s Kant, Bünyami̇n Akgül, Ayten Nalbant Aldanmaz

Turkish Journal of Biology

Apoptosis can be used to manipulate host cells by bacterial products such as bacterial heat shock proteins (Hsp). One of the virulence factors of periodontal pathogen Aggregatibacter actinomycetemcomitans is heat shock protein GroEL (AaGroEL), which has been shown to interact with host cells. AaGroEL (Hsp64) also has the potential to modulate immune system cells. In this study we used endogenous AaGroEL protein as an antigen to study bacterial Hsp-induced apoptosis in different immune system cells. Human peripheral blood mononuclear cells and cell lines were cultured with different doses (50-1000 ng/mL) of endogenous AaGroEL at various time points. Apoptosis of the …

Melatonin Induces Antiproliferative Activity Through Modulation Of Apoptoticpathway In H-Ras Oncogene Transformed 5rp7 Cells, Ayşe Kaplan, Gülşen Akalin Çi̇ftçi̇, Hati̇ce Mehtap Kutlu

Turkish Journal of Biology

In the present study, cytotoxic and apoptotic effects of melatonin were investigated on H-ras oncogene transformed rat embryo fibroblast 5RP7 cells. Melatonin inhibited cell growth and induced apoptosis in 5RP7 cells. We showed inhibition of cell proliferation that was time- and dose-dependent in 5RP7 cells for 24 and 48 h. Melatonin was not toxic in NIH/3T3 primary mouse embryonic fibroblast cells at low doses for 24 and 48 h. The IC50 (380 μM) value of melatonin for 48 h was chosen for advanced assays. The percentages of early/late apoptotic cells to which melatonin (IC50: 380 μM) was administered were increased …