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Charakterisierung eines ribosomenassoziierten Proteinkomplexes der Hefe Saccharomyces cerevisiaeBerlin 09 November 2001 (has links) (PDF)
No description available.
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Myosin Va mutation in rats is an animal model for the human hereditary neurological disease, Griscelli syndrome type 1Takagishi, Yoshiko, 高岸, 芳子, Murata, Yoshiharu 11 1900 (has links)
No description available.
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The role of the yeast GRD20 protein in membrane trafficking and actin organizationSpelbrink, Robert G. January 2000 (has links)
Thesis (Ph. D.)--University of Missouri-Columbia, 2000. / Typescript. Vita. Includes bibliographical references (leaves 130-155). Also available on the Internet.
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Role of Ca2+ -permeable cation channels in Ca2+ Signalling and necrotic cell deathWisnoskey, Brian J. January 2004 (has links)
Thesis (Ph. D.)--Case Western Reserve University, 2004. / [School of Medicine] Department of Physiology and Biophysics. Includes bibliographical references. Available online via OhioLINK's ETD Center.
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ER stress in the pathogenesis of osteochondrodysplasiaChan, Cheuk-wing, Wilson., 陳卓榮. January 2009 (has links)
published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy
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A study of biological role of reactive oxygen species in cellular response in stressLam, Dennis, 林勁行 January 2012 (has links)
When proteins are unable to fold properly in the endoplasmic reticulum (ER), the
resultant formation of misfolded proteins causes stress of the ER. Cells with ER stress
often have a higher abundance of reactive oxygen species (ROS). Previous studies
suggest that ROS could aggravate ER stress by further disrupting the ER protein
folding process. More recent studies suggest that the unfolded protein response
signaling pathways activated by ER stress could lead to the production of ROS. Such
studies lead to the hypothesis that ER stress could be promoted by ROS, and vice
versa. The aim of the present study is to test the above hypothesis by studying how
ROS could be generated in ER-stressed cells. This is followed by investigating if ROS
could increase or decrease the level of ER stress in cells. Finally, the extent of ER
stress induced cell death in the presence and absence of ROS is assessed.
The treatment of HeLa cells with tunicamycin (Tm), a common ER-stress
inducing agent, resulted in the elevation of intracellular ROS that could be detected
with the ROS-reactive probe dichlorodihydrofluorescein (DCF), but not
dihydroethidium which is relatively specific towards superoxide anion. The
Tm-induced elevation of ROS could be prevented by co-incubation of cells with thiol
reductants such as dithiothreitol and N-acetylcysteine but not with the free radical
scavenger ascorbate. The tunicamycin-induced elevation of ROS level could also be
prevented by the over-expression of catalase in HeLa. These data is consistent with
the idea that hydrogen peroxide is a major form of ROS produced in Tm-treated cells.
In addition to elevation of ROS level, HeLa cells treated with tunicamycin also
resulted in the phosphorylation of PERK and eIF2α, and the splicing of XBP-1. In the
presence of cycloheximide to inhibit protein synthesis so as to deplete protein
substrates for folding in the ER, tunicamycin-induced ER stress was greatly
minimized as was evident by the absence of both the phosphorylation of PERK and
splicing of XBP-1. However, the phosphorylation of eIF2α and elevation of
DCF-detectable ROS remained unaffected. The cycloheximde-resistant
phosphorylation of eIF2α could be prevented when cells were co-treated with thiol
reductants, or upon the over-expression of catalase. These data suggest that the
production of ROS in Tm-treated cells does not require the presence of ER stress as a
prerequisite. Furthermore, the ROS so produced could induce phosphorylation of
eIF2α without the need to cause ER stress in the first place.
The quenching of ROS through the use of thiol reductants, or the over-expression
of catalase, had no effect on inhibition of protein synthesis in cells treated with
tunicamycin. However, the extent of cell death was significantly increased. The data
obtained in this study is not consistent with the idea that ROS is a downstream
product of ER stress, capable of inducing more ER-stress by a feedback mechanism.
Therefore, a mutually enhancing effect between ER stress and ROS may not exist.
The ROS found in stressed cells may serve to extend cellular survival under the
condition of continuous stress. / published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy
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Role(s) of p53/p63 in chondrocyte re-differentiation upon activation of ER stressPei, Lim-cho, Steven, 貝念祖 January 2012 (has links)
Endoplasmic Reticulum (ER) stress signal is a cellular response to various insults including
abnormal protein folding load, activating the unfolded protein response. Under severe ER stress,
apoptosis will occur in most cell types. Interestingly, this does not happen in a disease model for
Metaphyseal chondrodysplasia type Schmid (MCDS), where ER stress was activated in the
hypertrophic zone of the growth plate where mutant collagen X proteins that cannot be folded
correctly is expressed. Instead of normal progression from proliferating chondrocytes (PCs) to
hypertrophic chondrocytes (HCs) and conversion to bone, HCs in MCDS mice undergo
re-differentiation to PCs as a survival strategy due to an activation of ER stress. Transcription
factors are known to be important in regulating differentiation. p53 family members, as
transcription factors, are known to play important roles in developmental processes including
cellular reprogramming, thus, we hypothesize that the ectopic expression of key transcription
factors, p53 and TAp63, which are activated by ER stress is involved in HC re-differentiation. p53
is normally expressed in late PCs, Pre-HCs, and upper HCs, while TAp63 is expressed in PCs and
Pre-HCs suggesting they may have roles in chondrocyte differentiation. p53 activated under ER
stress in HCs are nuclear localized in MCDS mice, but did not invoke the apoptotic programme.
In this project, using quantitative analyse to study the expression level of p53 and p63 isoforms, it
was confirmed that p53 and TAp63γ are in part transcriptionally activated upon ER stress. From
functional study by inactivating p53 in MCDS mice, it was shown that p53 alone was not sufficient
to mediate re-differentiation. Given that TAp63γ isoforms is also highly upregulated upon ER
stress, and the negative regulator, ΔNp63, is downregulated, this combination of change in gene
expression also need to be considered.
Furthermore, known regulators of p53 and p63 activity such as ASPP1 and iASPP are also
differentially expressed in HCs, and are altered upon activation of ER stress favouring cell survival.
Thus, it would be important to evaluate the combination of TAp63 in the re-differentiation process
from conditional inactivation of p63 or in combination with p53 to gain a clearer understanding of
the contribution and relationship of these transcription factors in the survival strategy of stressed
HCs. / published_or_final_version / Biochemistry / Master / Master of Philosophy
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The anticancer effects of vitamin E derivative alpha-tea in human hematological malignanciesLu, Na, 1978- 16 February 2011 (has links)
alpha-TEA (alpha-tocopherol ether linked acetic acid) has been shown to induce apoptosis in human prostate, ovarian and breast cancer cells in culture and in xenograft models by promoting pro-apoptotic pathways and inhibiting anti-apoptotic pathways. Studies investigated the ability of alpha-TEA to induce apoptosis in human hematological malignant cell lines Jurkat, Raji and U266, representing T cell leukemia, B cell lymphoma and multiple myeloma, respectively. The three cell lines were cultured in the presence of different concentrations of alpha-TEA for different time periods, and examined for apoptosis by annexin V – FITC analyses, DAPI staining, and western blotting for poly (ADP-ribose) polymerase cleavage. alpha-TEA induced apoptosis in all three cell lines in a dose and time dependent manner. Levels of pro-apoptotic molecules DR5, c-Jun N-terminal protein kinase (JNK), C/EBP homologous protein (CHOP), caspase 9, and caspase 3 were upregulated in alpha-TEA treated cells in comparison to vehicle controls. Caspase 8 was activated in Jurkat and U266 cells but not in Raji cells. Apoptosis and pro-death signaling mediators were blocked by ceramide inhibitor, desipramine. The anti-apoptotic nuclear factor kappa B (NF-[kappa]B) signaling pathway was down-regulated in alpha-TEA treated Raji and U266 cells. Combinations of omega-3 fatty acid docosahexaenoic (DHA) and alpha-TEA significantly enhanced apoptosis in Jurkat cells in comparison to single treatments and vehicle control. In summary, alpha-TEA induced apoptosis in the malignant hematological cell lines is via shared and distinct pathways. ASMase/ceramide-mediated JNK activation and endoplasmic reticulum (ER) stress mitochondrial dependent apoptosis are involved in alpha-TEA induced apoptosis in the three cell lines; however, the cell lines exhibit cell type-specific responses to alpha-TEA: activation of death receptor/caspase 8 pathway is involved in Jurkat cells, suppression of NF-[kappa]B signaling is involved in Raji cells, and the U266 cells share both of these pathways for the induction of apoptosis. / text
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DIMERIZATION IS REQUIRED FOR THE TRANSACTIVATION FUNCTION OF LUMAN BUT NOT FOR ITS ACTIVATION BY PROTEOLYTIC CLEAVAGEMcCluggage, Adam Robert Russell 21 December 2011 (has links)
Luman (LZIP/CREB3) is a basic leucine zipper (bZIP) transcription factor that has been linked to the endoplasmic reticulum (ER) stress response. In the event of ER stress, Luman is proteolytically cleaved, or ‘activated’, through regulated intramembrane proteolysis (RIP), resulting in an amino-terminal fragment that translocates to the nucleus to activate transcription of downstream unfolded protein response (UPR)-related genes. The general mode of activation of the key signal transducers of the UPR appears to be an alteration of their oligomeric states. Structural and functional similarities to these proteins suggest that Luman may be activated in a similar manner.
In this thesis, we demonstrate through in vitro and in vivo studies that Luman can form homodimers in the cell. Through the use of mutagenesis, we show that Luman dimerization is mediated through the leucine zipper and we provide evidence that Luman dimerization is required for its transcription activation function. However, we found that Luman dimerization is not required for its activation by proteolytic cleavage.
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Endoplasmic reticulum stress induction by an endogenous retrovirus glycoprotein during neuroinflammation: regulation by a free radical scavengerDeslauriers, Andre Unknown Date
No description available.
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