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Articles 1 - 21 of 21
Full-Text Articles in Molecular Biology
Simvastatin Induces Autophaghy-Mediated Cell Death In Metastatic Breast Cancer Cells, Jessica Allagoa
Simvastatin Induces Autophaghy-Mediated Cell Death In Metastatic Breast Cancer Cells, Jessica Allagoa
Theses (2016-Present)
Breast cancer remains one of the leading causes of cancer deaths among women. Due to the limited effectiveness of current anticancer drugs, ongoing research has extended towards alternative drug categories for potential treatments. Recent findings indicate that statins possess the ability to suppress tumors across various cell types. Traditionally, statins are known as a class of cholesterol-lowering agents and function by inhibiting 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, a key enzyme in the mevalonate pathway. However, statins can also suppress cell proliferation and ultimately lead to cell death, which includes Type I apoptosis-induced cell death or Type II autophagy-induced cell death. Autophagy is …
Ellagic Acid Inhibits Α-Synuclein Propagation And Alleviates The Neurotoxicity By Enhancing Autophagic Flux In Animal Model Of Parkinson’S Disease, Nada Akram Abdellatif
Ellagic Acid Inhibits Α-Synuclein Propagation And Alleviates The Neurotoxicity By Enhancing Autophagic Flux In Animal Model Of Parkinson’S Disease, Nada Akram Abdellatif
Theses
Parkinson’s Disease (PD) is the second most common neurological disorder pathologically characterized by loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNc) as well as the formation of Lewy bodies composed mainly of α-synuclein (α-syn) aggregates. It has been documented that abnormal aggregation of α-syn is one of the major causes of developing PD. Ellagic Acid (EA) is a widely known dietary supplement found in pomegranates as well as a plethora of berries and nuts. EA has been shown to prevent α-syn aggregates’ toxicity in cellular model of PD. In the current study we aim to evaluate whether …
Med13 Degradation Defines A New Receptor-Mediated Autophagy Pathway Activated By Nutrient Deprivation, Sara E. Hanley
Med13 Degradation Defines A New Receptor-Mediated Autophagy Pathway Activated By Nutrient Deprivation, Sara E. Hanley
Graduate School of Biomedical Sciences Theses and Dissertations
Cells are exposed to an enormous amount of diverse extracellular cues but have a limited arsenal of weapons for protecting and maintaining homeostasis. To overcome these restrictions, nature has engineered proteins that have multiple functions. The pleiotropy of using one protein to carry out a variety of functions allows cells to rapidly execute tailored responses to a diverse set of signals. The Cdk8 kinase module (CKM) is a conserved detachable unit of the Mediator complex predominantly known for its role in transcriptional regulation. The CKM is composed of four proteins, the scaffolding proteins Med13 and Med12, as well as the …
Characterization Of The Full-Length Bag3 Protein And Stress Induced Formation Of Bag3-Z, Ahmed Gamal Abdalla Zied
Characterization Of The Full-Length Bag3 Protein And Stress Induced Formation Of Bag3-Z, Ahmed Gamal Abdalla Zied
Master's Theses
Bcl2-associated athanogene-3 (BAG3) is a pro-autophagy co-chaperone that we havepreviously shown localizes to the cardiac sarcomere and is critical for proteostasis and maintenance of normal sarcomeric function. Indeed, BAG3 loss in heart failure (HF) results in accumulation of ubiquitinated sarcomeric proteins, and depressed maximum force generating capacity (Fmax). However, how BAG3 is regulated in the cell is not well understood, with uncertainty about its structure and proteoforms. During our analysis of human heart tissue, BAG3 appears as a “doublet”, with one band at 74 kDa (BAG3-Z) and a second at a higher 85 kDa (BAG3-FL). Previous studies hypothesized the full-length …
Calmodulin Like 38 Is Required For Autophagy Of Hypoxia-Induced Cytoplasmic Rna Granules In Arabidopsis Thaliana, Sterling Field
Calmodulin Like 38 Is Required For Autophagy Of Hypoxia-Induced Cytoplasmic Rna Granules In Arabidopsis Thaliana, Sterling Field
Doctoral Dissertations
In response to the energy crisis resulting from submergence stress and hypoxia, the model plant Arabidopsis thaliana limits non-essential mRNA translation, and accumulates cytosolic stress granules. Stress granules are phase-separated mRNA-protein particles that partition transcripts for various fates: storage, degradation, or return to translation after stress alleviation. Another response by the plant cell to low oxygen stress is the induction of the turnover pathway autophagy. Stress granule regulation by autophagy occurs by a ‘granulophagy’ pathway in yeast and mammalian systems through which parts or whole stress granules are degraded. Whether this occurs in plants has not been investigated.
A connection …
Post-Translational Modification And Degradation Mechanisms Of The Aryl Hydrocarbon Receptor, Yujie Yang
Post-Translational Modification And Degradation Mechanisms Of The Aryl Hydrocarbon Receptor, Yujie Yang
University of the Pacific Theses and Dissertations
The aryl hydrocarbon receptor (AHR) is a transcription factor first discovered to be activated by exogenous ligands, such as dioxins, and helps promote downstream gene (e.g. CYP1A1) transcription to metabolize the toxicants. With the reports of various AHR targets genes, the expression levels and activities of AHR have been implicated in many physiological and pathological situations. Understanding how AHR protein level is regulated would provide more information to target AHR. AHR stays in the cytosol in the absence of ligand in a complex with HSP90, p23 and XAP2. After ligand activation, AHR translocates into the nucleus, fulfilling its transactivation function …
Ionic Mechanism Of Lysosomal Function And Cell Metabolism, Jian Xiong
Ionic Mechanism Of Lysosomal Function And Cell Metabolism, Jian Xiong
Dissertations & Theses (Open Access)
Two Pore Channels (TPCs) are endolysosomal ion channels that are permeable to sodium and calcium. Defects in TPCs have been implicated to impair vesicle trafficking, autophagy and cell metabolism control; however, the detailed mechanism remains largely unknown. In this study, I show that TPCs are critical for appropriate cargo delivery to the lysosomes and deletion of either TPC1 or TPC2 leads to delayed clearance of autophagosomes, resulting in enlarged lysosomes and accumulated contents inside the lysosomes. Cells with both TPC deleted also exhibit 50% reduction in lysosomal amino acids under normal culture conditions, leading to reduced homeostatic mTORC1 activation.
Glutamine …
Cloning And Expression Of Human Synaptosome Associated Protein 29 In E. Coli, Logan M. Ryals
Cloning And Expression Of Human Synaptosome Associated Protein 29 In E. Coli, Logan M. Ryals
Honors Theses
Acting as the chief mediators of vesicular fusion, soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) play a role in many intracellular trafficking events by moving opposing membranes into close proximity. One such event takes place in the process of autophagy. A key SNARE involved in autophagy is Synaptosome Associated Protein 29 (SNAP-29), which acts on the autophagosome membrane to promote autophagosome and lysosome fusion. Kaposi’s Sarcoma Herpesvirus (KSHV) proteins ORF33 and ORF38 were demonstrated to interact with SNAP-29. The exact mechanism of this interaction is yet to be elucidated but it is hypothesized that these interactions allow KSHV to modulate …
Novel Post-Translational Modification And Function Of Fus: The Relevance To Amyotrophic Lateral Sclerosis, Alexandra Arenas
Novel Post-Translational Modification And Function Of Fus: The Relevance To Amyotrophic Lateral Sclerosis, Alexandra Arenas
Theses and Dissertations--Toxicology and Cancer Biology
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by the preferential death of motor neurons. Approximately 10% of ALS cases are familial and 90% are sporadic. Fused in Sarcoma (FUS) is a ubiquitously expressed RNA binding protein implicated in familial ALS and frontotemporal dementia (FTD). FUS is ubiquitously expressed in cells and has a variety of functions in the nucleus and cytoplasm. FUS mutations in the nuclear localization sequence (NLS) causes mislocalization of FUS in the cytoplasm, where it can undergo liquid-liquid phase separation and become stress granules or protein inclusions. Although FUS inclusion bodies can be found in …
Investigating Autophagy Dysfunction Induced By A Parkinson's Disease-Causing Mutation In Vps35, Abir Ashfakur Rahman
Investigating Autophagy Dysfunction Induced By A Parkinson's Disease-Causing Mutation In Vps35, Abir Ashfakur Rahman
Boise State University Theses and Dissertations
Parkinson’s Disease (PD) is an idiopathic disorder with no known cure. With number of cases steadily rising around the world, it is imperative to turn to the underlying cellular and molecular mechanisms of the disease manifestation and neurodegeneration to craft novel modes of therapy. VPS35 is one of the few genes that have identified and definitively linked to familial PD. The particular mutation that has been associated is known to cause dysfunction of a key cellular process known as autophagy. This process is primarily responsible for clearance of unwanted, damaged or misfolded proteins, among other things. Our study reveals an …
Mechanisms Adopted By Dengue-2 Viruses To Induce Autophagy In Mammalian Cells, Sounak Ghosh Roy
Mechanisms Adopted By Dengue-2 Viruses To Induce Autophagy In Mammalian Cells, Sounak Ghosh Roy
Dissertations, Theses, and Capstone Projects
Dengue, the most rapidly spreading flavivirus, threatens to affect almost half of the human global population. We previously showed that dengue-2 protects canine kidney cells (MDCK) from cytotoxic chemicals. We showed, independently, that cell protection, as well as viral replication and maturation, are positively regulated by PI3K-dependent autophagy. However, we had not identified the specific pathway that induces autophagy in infected cells. The current study explores the role of a specific branch of the endoplasmic reticulum (ER) stress-mediated Unfolded Protein Response (UPR), the PERK/eIF2α/ATF4 pathway in the induction of autophagy by …
Syk Promotes Tgf-Beta-Induced P-Body Clearance In Breast Cancer Cells Through The Enhancement Of Autophagy, Shana D. Hardy
Syk Promotes Tgf-Beta-Induced P-Body Clearance In Breast Cancer Cells Through The Enhancement Of Autophagy, Shana D. Hardy
Open Access Dissertations
SYK is a protein tyrosine kinase that plays an essential role in the development and activation of immune cells. Its expression, however, is not limited to immune cells. SYK is expressed in a variety of epithelial cell types and epithelial-derived tumors. Reports regarding the role of SYK expression in these diverse cell types and tumors have been opposing. In breast cancer, SYK expression has been overwhelmingly associated with tumor suppression. The loss of Syk expression is observed in invasive breast carcinoma tissue and cell lines and the reintroduction of Syk into metastatic breast cancer cells suppresses tumor growth and metastasis. …
Inhibiting The Interaction Between Grp94 And Myocilin To Treat Primary Open-Angle Glaucoma, Andrew Stothert
Inhibiting The Interaction Between Grp94 And Myocilin To Treat Primary Open-Angle Glaucoma, Andrew Stothert
USF Tampa Graduate Theses and Dissertations
Glaucoma is a neurodegenerative protein misfolding disorder classified by increases in IOP, damage to retinal ganglion cells (RGCs), optic nerve (ON) head damage, and progressive irreversible blindness. Primary open-angle glaucoma (POAG) is the most common form of glaucoma, constituting over 90% of clinical cases. POAG is observed in patients where normal outflow channels, mainly the trabecular meshwork (TM), are exposed at the angle formed by the iris and cornea. However, due to TM cellular dysfunction, aqueous outflow resistance is increased preventing normal circulation of aqueous humor. Recent studies have shown that in 2-4% of POAG cases, increased intracellular levels of …
Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung
Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung
Open Access Dissertations
In neurons, normal distribution and selective removal of mitochondria are essential for preserving compartmentalized cellular function. Parkin, an E3 ubiquitin ligase associated with familial Parkinson’s disease, has been implicated in mitochondrial dynamics and removal. However, it is not clear how Parkin plays a role in mitochondrial turnover in vivo, and whether the mature neurons possess a compartmentalized Parkin-dependent mitochondrial life cycle. Using the live Drosophila nervous system, here, I investigate the involvement of Parkin in mitochondrial dynamics; organelle distribution, morphology and removal. Parkin deficient animals displayed less number of axonal mitochondria without disturbing organelle motility behaviors, morphology and metabolic state. …
Leptin Regulates The Expression Of Autophagy-Related Genes In Chickens, Peter Olawale Ishola
Leptin Regulates The Expression Of Autophagy-Related Genes In Chickens, Peter Olawale Ishola
Graduate Theses and Dissertations
Autophagy or cellular self-digestion, a lysosomal degradation pathway that is conserved from yeast to human, plays a key role in recycling cellular constituents, including damaged organelles. It also plays a pivotal role in the adaptation of cells to a plethora of distinct stressors including starvation. Autophagy has been extensively studied in mammals and yeast, but little is known in avian species. Thus, the major objective of the present study was to determine the effects of leptin on autophagy-related genes in chicken hypothalamus, muscle and liver. Leptin is an adipocytokine that is mostly produced by white adipose cells in mammals (as …
Autophagy And Its Potential Role In Stress And Feed Efficiency Using Avian Lines, Alissa Laura Piekarski
Autophagy And Its Potential Role In Stress And Feed Efficiency Using Avian Lines, Alissa Laura Piekarski
Graduate Theses and Dissertations
Autophagy is a highly conserved cellular mechanism that is responsible for the degradation and recycling of damaged organelles. Recently, autophagy has been involved in critical roles during overall development of the organism and degradation of damaged cellular components. This pathway has witnessed dramatic growth in the last few years and has been extensively studied in yeast and mammals, however, there is a paucity of information in avian (non-mammalian) species. First, we characterized genes involved in the autophagy pathway in male and female Jungle Fowl to determine gender and tissue specific differences. Secondly, tissue and genotype differences in Japanese quail selected …
A Protective Role Of Autophagy In A Drosophila Model Of Friedreich's Ataxia (Frda), Luan Wang
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 …
Cardiolipin Regulates Mitophagy Through The Pkc Pathway, Zheni Shen
Cardiolipin Regulates Mitophagy Through The Pkc Pathway, Zheni Shen
Wayne State University Dissertations
Cardiolipin (CL), the signature phospholipid of mitochondrial membranes, is important for cardiovascular health. Perturbation of CL metabolism is implicated in cardiovascular disease (CVD). The link between CL and CVD may be explained by the physiological roles of CL in pathways that are cardioprotective, such as autophagy/mitophagy and the mitogen-activated protein kinase (MAPK) pathways. My dissertation work focuses on elucidating how CL influences mitophagy and MAPK pathways.
crd1Δ was synthetically lethal/sick with the general autophagy mutants atg8Δ, atg18Δ and mitophagy mutant atg32Δ, suggesting that autophagy/mitophagy may be deficient in cells lacking CL. Microscopic examination of mitophagy revealed decreased translocation of GFP-tagged …
Potential Targeted Therapeutic Strategies For Overcoming Resistance In Braf Wild Type Melanoma, Vito William Rebecca
Potential Targeted Therapeutic Strategies For Overcoming Resistance In Braf Wild Type Melanoma, Vito William Rebecca
USF Tampa Graduate Theses and Dissertations
Melanoma manifests itself from the malignant transformation of melanocytes and represents the deadliest form of skin cancer, being responsible for the disproportionate majority of all skin cancer deaths. The 2002 discovery that 50% of all melanoma patients possess activating BRAF mutations ignited a significant paradigm shift in the way the melanoma field approached research and how patients were treated [1]. The era of targeted therapy had begun and with it came successful targeted BRAF inhibitor therapy regimens, which have accomplished improved clinical benefit (response rate, progression free survival, and overall survival) compared with treatment with chemotherapy in three phase III …
Signals Delivered By Interleukin-7 Regulate The Activities Of Bim And Jund In T Lymphocytes, Shannon Moore Ruppert
Signals Delivered By Interleukin-7 Regulate The Activities Of Bim And Jund In T Lymphocytes, Shannon Moore Ruppert
Electronic Theses and Dissertations
Interleukin-7 (IL-7) is an essential cytokine for lymphocyte growth that has the potential for promoting proliferation and survival. While the survival and proliferative functions of IL-7 are well established, the identities of IL-7 signaling components in pathways other than JAK/STAT, that accomplish these tasks remain poorly defined. To this end, we used IL-7 dependent T-cells to examine those components necessary for cell growth and survival. Our studies revealed two novel signal transducers of the IL-7 growth signal: BimL and JunD. IL-7 promoted the activity of JNK (Jun N-terminal Kinase), and that JNK, in turn, drove the expression of JunD, a …
Molecular Mechanism Of Agc Kinases In Human Malignant, Shaokun Shu
Molecular Mechanism Of Agc Kinases In Human Malignant, Shaokun Shu
USF Tampa Graduate Theses and Dissertations
The maintenance of normal cell function and tissue homeostasis is dependent on the precise regulation of multiple signaling pathways that control cellular decisions to either proliferate, differentiate, arrest cell growth, or initiate programmed cell death (apoptosis). Cancer arises when clones of mutated cells escape this balance and proliferate inappropriately without compensatory apoptosis. Deregulated cell growth occurs as a result of perturbed signal transduction that modulates or alters cellular behavior or function to keep the critical balance between the rate of cell-cycle progression (cell division) and cell growth (cell mass) on one hand, and programmed cell death (apoptosis, autophagy) on the …