In the physiologic contexts of embryonic development and tissue renewal, or as a pathologic response to cell injury and infectious pathogens, cell deaths are orchestrated for multiple. Pdf cell death and the subsequent postmortem changes, called necrosis, are integral parts of normal development and maturation cycle. The cell death process and the removal of the dying cells has to be tightly regulated since dysregulated cell death and cell clearance pathways are correlated with. Apoptosis or programmed cell death is the predominant form of physiological cell death by which the organism eliminates unnecessary or damaged single cells. Investigating the role of ptpn and entr1 in apoptotic. Gene expression profiling and the role of hsf1 in ovarian cancer in 3d spheroid models, trillitye paullin. Apoptosis is a form of programmed cell death that plays a central role in development and cellular homeostasis in higher eukaryotes. In this essay, we reexamine the warburg effect and establish a framework for understanding its contribution to the altered metabolism of cancer cells.
Lymphocyte apoptosis an overview sciencedirect topics. Inhibition of human mitochondrial peptide deformylase hspdf depolarizes the mitochondrial membrane, reduces mitochondrial protein translation and causes apoptosis in burkitts lymphoma. Crichton thesis submitted to the school of graduate and postdoctoral studies, university of ottawa, in partial fulfillment of the requirements for the degree of master of science department of biochemistry, microbiology and immunology. Around the time of this journals first volume, the concept of pcd, i. Typical apoptosis in animal cells must exhibit all of the following features. The most studied form of programmed cell death is apoptosis, a highly conserved, intrinsic process characterized by a family of proteases called caspases. Cellular injury arises when a cell is unable to sustain homeostasis. However, the underlying mechanisms are poorly understood.
Ptpn, a multipdz domain phosphatase, directly interacts with fas and low surface. Wayne state university cancer biology dissertations cancer. Submitted to the faculty of the university graduate school. Programmed cell death in development and defense plant. This disruption can result from uncontrolled cell growth or loss of a cells ability to undergo apoptosis. The overall aim of this thesis is to shed light on different aspects. Pdf cell death and the subsequent postmortem changes, called necrosis, are. In the first study, we found that sorafenib is particularly effective in inducing cell death in a panel of human myeloma cell lines. Undergraduate thesis or project rutledge patrick research. The cell death in midoogenesis is caspase dependent but is unusual in that it can occur independently of an initiator caspase.
On the one hand, accidental cell death is induced upon exposure to severe insults, such as mechanical, chemical or physical stimuli, which results in. Tnfinduced necroptosis involves a receptorbinding complex i that initiates prosurvival signaling, and an intracellular complex iib that activates. Nineteenth century research on naturally occurring cell death and related phenomena accepted. Characterization of polyadpribose par as a death signal. It has become commonplace to say that contemporary western society is deathdenying. The role of programmed cell death in the drought response of arabidopsis roots. Cell death is a highly organized fundamental activity that is equally complex in regulation as cell division and differentiation. This characterization, which sociologists have termed the denial of death thesis, first arose in the social. When the cell attempts to repair the dna damage, it can. Physiological basis of salt stress tolerance in rice expressing. Thesis submitted for the degree of doctor of philosophy at. Immunity article ripk1 and ripk3 kinases promote celldeathindependent in.
Here i present a thesis describing the mechanism and functions of a gene named spata2 that plays a dual role in regulating tnfinduced cell death as well as tlrmediated proinflammatory responses. Programmed cell death, the removal of certain cells, allows multicellular organisms the ability to sculpt developing tissue or protect themselves from disease. Experimental cell research ecr is dedicated to publishing manuscripts that significantly advance. Mar 01, 20 this thesis defines a new form of cancer cell death induced by the small molecule erastin. On the one hand, accidental cell death is induced upon exposure to severe insults, such as. Studies described in this thesis adopted genetic and pharmacological interventions, in conjunction with immunofluorescent and live cell imaging, to investigate trpm2dependent cell death induced by h2o2 and the 42residue of amyloid. The cell death process and the removal of the dying cells has to be tightly. However, the role of soluble fas and fasl in the proliferation and cell death of lung cancer cells has yet to be clarified and may open new opportunities for. It removes developing lymphocytes that fail to express an antigen receptor, thereby ensuring a functional repertoire of mature b and t cells, and it maintains tolerance toward self by eliminating lymphocytes with antigen receptors that recognize autoantigens. The rate of apoptotic cell formation was assumed to have a second order. A journey down the cell death pathway of mitochondria.
Molecular mechanisms of apoptosis induction by aicar and the. Functions of atrmec1 in meiosis and the cell cycle, layne weatherford. This research supports the idea that plant nblrr proteins can exert their effectormediated hr function without nuclear localization. However, the crosstalk between these two cell death related processes is not well understood in skeletal muscle. The role of mrgprx2mrgprb2 in regulating mast cell function, ibrahim s. Effects of chemotherapy on bone growth and chondrocyte. Par induces cell death via translocation of aif to the nucleus. Autophagy as a means of cell killing was first advanced by clarks phenotypic description of type ii autophagic cell death in 1990. Hoang, thi my linh 2014 engineering salinity tolerance in rice by exogenous expression of cell death regulators. Diminishment of photodynamic therapy by tumor incisions is not due to differences in acute cell death.
Mechanisms of ionizing radiationinduced cell death in primary lung cells ronald allan m. Tethering lov1 irreversibly to the plasma membrane with a dual acylated nterminal tag did not impact its ability to mediate hr cell death, reinforcing the idea that lov1 signaling occurs at the plasma membrane. Baehrecke center for biosystems research university of maryland biotechnology institute university of maryland, college park, md department of cancer biology. Cell biology, microbiology, and molecular biology theses and. Investigating the role of ptpn and entr1 in apoptotic cell. Pdf the role of programmed cell death in the drought. Whsc1l1 regulates estrogen receptor activity in sum44 breast cancer cells, jonathan curtis irish. A thesis submitted in conformity with the requirements for the degree of master of science. Msc by thesis submitted in fulfilment of the requirements for the degree of. Diminishment of photodynamic therapy by tumor incisions is. Erastin is a quinazolinone derivative that was originally identified in a screen for small molecules that are synthetic lethal with the ras oncogene. Cadmiuminduced autophagy and autophagic contribution to cell death in cadmiumtreated mesangial cells bilal ahmadi master of science department of laboratory medicine and pathobiology university of toronto 2016 abstract cadmium cd is a nephrotoxic metal that has a number of consequences for renal function. Classification of cell death fevziye vural, suna cebesoy and mehmet karakas abstract in 1972 kerr and colleagues collect the cell death under two headings.
How the dcp1 effector caspase becomes activated in midoogenesis remains to be determined. Dental theses penn dental medicine university of pennsylvania. Therapeutic approaches to halting photoreceptor cell death. Described decades ago, the warburg effect of aerobic glycolysis is a key metabolic hallmark of cancer, yet its significance remains unclear. Effects of chemotherapy on bone growth and chondrocyte cell. Sudeshna dutta, doctor of philosophy, 2008 dissertation directed by. Nineteenth century research on naturally occurring cell.
Inhibition of human mitochondrial peptide deformylase. To further understand how different species of par regulate the nuclear translocation of aif, we generated a parbinding mutant aif transgenic knockin mouse. Paradoxically, cell death helps shape an organisms life. Examining the role of autophagy in skeletal muscle cell death and differentiation by michael elliott mcmillan a thesis presented to the university of waterloo in fulfilment of the thesis requirement for the degree of doctor of philosophy in kinesiology waterloo, ontario, canada, 2014. Although cell death is known as apoptosis ve necrosis, molecular studies add to morphological studies and according to this, this. Cadmiuminduced autophagy and autophagic contribution to cell. During this time, however, ca1 cell death continued over the 90 day survival period p cell death and neuroplasticity recovery of function.
Molecular mechanisms of necrotic cell death in ischemic renal injury. This student paper was written as an assignment in the. Regulation of tumor necrosis factorinduced cell death and. We studied the lymphocyte apoptosis stage of infection in many different strains of mice. Kearney tcd thesis 10640 inflammatory consequences. A journey down the cell death pathway of mitochondriatargeted chlorambucil by rida mourtada a thesis submitted in conformity with the requirements for the degree of master of science graduate department of pharmaceutical sciences. Cadmiuminduced autophagy and autophagic contribution to cell death in cadmiumtreated mesangial cells bilal ahmadi master of science department of laboratory medicine and pathobiology university of toronto 2016 abstract cadmium cd is a nephrotoxic metal. Targeting tbet for prevention of graftversushost disease and leukemia relapse after allogeneic hematopoietic stem cell transplantation, jianing fu.
This was 7 decades before the flurry of apoptosis research in animals. Victorin induces apoptoticlike cell death, and cell death is a component of resistance to p. Pdf amelioration of ionizing radiation induced cell death. In presenting this thesis in partial fulfillment of the requirements of a postgraduate degree. Tumor necrosis factor tnf is an apical cytokine that drives inflammation through triggering the synthesis and secretion of multiple downstream proinflammatory cytokines and chemokines. Molecular mechanisms of cell death and cell clearance. Engineering salinity tolerance in rice by exogenous.
Page 4 of 26 due to its importance in such various biological processes, programmed cell death is a widespread phenomenon, occuring in all kinds of metazoans tittel, 2000 such as in mammals, insects. Vdrripk1 interaction and its implications in cell death and cancer intervention, waise quarni. Apoptosis, or cell suicide, is the mechanism by which old or damaged cells normally selfdestruct. Necrotic cell death, as one type of major cell death after ischemic reperfusion injury. Examining the role of autophagy in skeletal muscle cell death. Kim newton, andreas strasser, in advances in immunology, 2001. It is well known that several cancers exhibit a decreased cell surface expression of fas and consequently escape the control of fasmediated apoptosis, although underlying mechanisms are unclear. Studies on the mechanisms of sorafenibinduced cell death. Germline cell death in drosophila occurs in response to many stimuli and uses diverse mechanisms, both apoptotic and nonapoptotic. Apoptosis is a canonical cellular death pathway that.
Once perceived as an unimportant occurrence in living organisms, cell degeneration was reconfigured as an important biological phenomenon in development, aging, health, and diseases in the twentieth century. Emphasis was put on the exposure of phosphatidylserine ps a well studied eatme signal that is known to facilitate recognition and engulfment of dying cells by phagocytes and is known to be an. Almost all the treatments that increased apoptosis following infection were essential early innate. When the cell attempts to repair the dna damage, it can occasionally do so through an. The overall aim of this thesis is to shed light on different aspects regarding the mechanisms of programmed cell death and cell clearance. The viable cell population was assumed to consist of normal growing, normal nongrowing and apoptotic cell subpopulations. Types of cell death according to the nomenclature committee on cell death, cell death can be operationally categorized in two major groups. Cell death and its regulation molecular cell biology. More than 100 nineteenth century publications deal with it, and we re view most of these. But since necrosis refers to the degradative processes that occur after cell death, it is considered by some to be an inappropriate term to describe a mechanism of cell death. Characterization of colon cancer cell culture based. In our study, we determined changes in expression of genes related to.
Ripk1 and ripk3 kinases promote celldeathindependent. Identifying mechanisms of resistance and potential therapeutic targets for pediatric acute myeloid leukemia, john timothy caldwell. Regina day, phd, associate professor, department of pharmacology and graduate program in molecular and cell biology exposure to high doses of ionizing radiation ir causes serious biological. The demise of cells by programmed cell death is marked by a welldefined sequence of morphological changes, collectively referred to as apoptosis, a greek word that means dropping off or falling off as in leaves from a tree. Molecular mechanisms of apoptosis induction by aicar and. Lymphocyte apoptosis is crucial to proper immune function. Cadmiuminduced autophagy and autophagic contribution to. This student paper was written as an assignment in the graduate course free radicals in biology and medicine 77. The main aim of this thesis is to investigate the anticancer effects of the multi tyrosine kinase inhibitor tki sorafenib in hematological and solid tumors. However, this phenomenon later came into question, because the presence of autophagosomes in dying cells does not necessarily signify that autophagy is the cause of demise, but rather may reflect the efforts of the cell to prevent it.
Study of the physiological and molecular mechanisms underlying peptideinduced cell death and biofilm formation in streptococcus mutans julie ann perry doctor of philosophy, faculty of dentistry, university of toronto 2009 abstract biofilms are complex and highly adapted communities of microorganisms found attached to surfaces. The role of brctcontaining proteins brca1 and paxip1 in cancer, ankita jhuraney. Additionally, treatments with monoclonal antibodies specific to various cytokines and cytokine receptors were tested. School of genetics and microbiology, 2001, pp 260 download item. The role 18ffdg and 18fnaf petct in assessment of temporomandibular joint metabolic activity in rheumatoid arthritis, abdulrahman a. Physiological cell death has been observed in various multicellular organisms. Engineering salinity tolerance in rice by exogenous expression of cell death regulators i engineering salinity tolerance in rice by exogenous expression of cell death regulators. Programmed cell death pcd is a naturally occurring event in multicellular organisms. The main objective of this study was to develop an in vitro cell culture. The significance of apoptosis the development and maintenance of multicellular biological systems depends on a sophisticated interplay between the cells forming the organism, it sometimes even seems to involve an altruistic. Programmed cell death in plants refers to the apoptoticlike cell death which is under the strict genetical control. Examining the role of autophagy in skeletal muscle cell. Cell death signaling complexes during macrophage differentiation. Inflammatory consequences of divergent cell death signals.
Dying cells shrink and condense and then fragment, releasing small membranebound apoptotic bodies, which. It is part of the development as well as ensuring tissue homeostasis and cellular turnover. Death receptor fascd95 is a crucial component in the regulation of ligand induced apoptosis in many cell types. Whalen,9 manolispasparakis,8 siddharthbalachandran,4 michelle kelliher,3 alexander poltorak,6 and alexei. This dissertation tells a twentiethcentury history of scientific investigations on cell degeneration, including cell death and aging. Engineering salinity tolerance in rice by exogenous expression of cell death regulators v list of publications and conferences thi my linh hoang, brett williams, harjeet khanna, james dale and sagadevan g. The fact that cell death is not ultimately a bad thing came as a surprise to many researchers. Amelioration of ionizing radiation induced cell death in lymphocytes by baicalein thesis pdf available june 2016 with 3,779 reads how we measure reads. Cell death signaling complexes during macrophage differentiation dikchha rijal thesis submitted to the faculty of graduate and postdoctoral studies in partial fulfillment of the requirements for the msc degree in microbiology and immunology department of biochemistry, microbiology and immunology faculty of medicine, university of ottawa. Metabolic analysis of a cho cell line in batch and fedbatch. Trpm2 channelmediated signalling mechanisms for neuronal. Thus, the purpose of my research was to characterize victorininduced cell death to provide insight into both disease susceptibility and resistance.
Competing processes of cell death and recovery of function. Thi my linh hoang thesis pdf 5mb description rice, an important crop that feeds more than half of the worlds population is very sensitive to salinity stress a growing. The nanotoxicology discipline deals with the nanoparticle npinduced toxicity and mechanisms of cell death in healthy cells, whereas anticancer agents delivered via nanobased approaches aim to induce cell death in abnormally proliferating cancer cells. Autophagydependent cell death where, how and why a cell. Nanotoxicology and anticancer nanotherapeutics are essentially two sides of the same coin.
Induction of stroke via middle cerebral artery occlusion mcao is used to detect the parinduced cell death. The alternative to apoptotic cell death is necrosis, which is considered to be a toxic process where the cell is a passive victimandfollowsanenergyindependentmodeofdeath. Study of the physiological and molecular mechanisms. Hypersensitive cell death is commonly controlled by direct or indirect interactions between pathogen. Cell biology, microbiology, and molecular biology theses. Interestingly, both apoptotic signaling and altered autophagy have been observed in states associated with muscular atrophy and dysfunction.
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