scholarly journals Presenilin 1 Regulates [Ca2+]i and Mitochondria/ER Interaction in Cultured Rat Hippocampal Neurons

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Eduard Korkotian ◽  
Anna Meshcheriakova ◽  
Menahem Segal
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Survival Rate ◽  
Hippocampal Neurons ◽  
Presenilin 1 ◽  
Abrupt Increase ◽  
Lower Survival Rate ◽  
Neuronal Functions ◽  
Mushroom Spines

Mutations in the presenilin 1 (PS1) gene are a major trigger of familial Alzheimer’s disease (AD), yet the mechanisms affected by mutated PS1 causing cognitive decline are not yet elucidated. In the present study, we compared rat hippocampal neurons in culture, transfected with PS1 or with mutant (M146V) PS1 (mPS1) plasmids in several neuronal functions. Initially, we confirmed earlier observations that mPS1-expressing neurons are endowed with fewer mature “mushroom” spines and more filopodial immature protrusions. The correlation between calcium changes in the cytosol, mitochondria, and endoplasmic reticulum (ER) is mitigated in the mPS1 neurons, tested by the response to an abrupt increase in ambient [Ca2+]o; cytosolic [Ca2+]i is higher in the mPS1 neurons but mitochondrial [Ca2+] is lower than in control neurons. Strikingly, mPS1-transfected neurons express higher excitability and eventual lower survival rate when exposed to the oxidative stressor, paraquat. These results highlight an impaired calcium regulation in mPS1 neurons, resulting in a reduced ability to handle oxidative stress, which may lead to cell death and AD.

Alginate oligosaccharide protects against endoplasmic reticulum- and mitochondrial-mediated apoptotic cell death and oxidative stress

Biomaterials ◽  
2011 ◽  
Vol 32 (23) ◽  
pp. 5438-5458 ◽  
Author(s):  
Solaleh Khoramian Tusi ◽  
Leila Khalaj ◽  
Ghorbangol Ashabi ◽  
Mahmoud Kiaei ◽  
Fariba Khodagholi
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Alginate Oligosaccharide ◽  
And Oxidative Stress

Effects of Alzheimer-related presenilin-1 mutations on oxidative stress and cell death in transgenic mice

2000 ◽  
Vol 21 ◽  
pp. 43
Author(s):  
Anne Eckert ◽  
Katharina Schindowski ◽  
Silke Leutner ◽  
Christian Luckhaus ◽  
Nathalie Touchet ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Transgenic Mice ◽  
Presenilin 1

scholarly journals Calcium and cell death signaling in neurodegeneration and aging

2009 ◽  
Vol 81 (3) ◽  
pp. 467-475 ◽  
Author(s):  
Soraya Smaili ◽  
Hanako Hirata ◽  
Rodrigo Ureshino ◽  
Priscila T. Monteforte ◽  
Ana P. Morales ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Apoptotic Cell ◽  
Essential Elements ◽  
Apoptotic Cell Death ◽  
Nuclear Fragmentation ◽  
Physiological Processes ◽  
Cell Death Signaling ◽  
Lines Of Evidence

Transient increase in cytosolic (Cac2+) and mitochondrial Ca2+ (Ca m2+) are essential elements in the control of many physiological processes. However, sustained increases in Ca c2+ and Ca m2+ may contribute to oxidative stress and cell death. Several events are related to the increase in Ca m2+, including regulation and activation of a number of Ca2+ dependent enzymes, such as phospholipases, proteases and nucleases. Mitochondria and endoplasmic reticulum (ER) play pivotal roles in the maintenance of intracellular Ca2+ homeostasis and regulation of cell death. Several lines of evidence have shown that, in the presence of some apoptotic stimuli, the activation of mitochondrial processes maylead to the release of cytochrome c followed by the activation of caspases, nuclear fragmentation and apoptotic cell death. The aim of this review was to show how changes in calcium signaling can be related to the apoptotic cell death induction. Calcium homeostasis was also shown to be an important mechanism involved in neurodegenerative and aging processes.

scholarly journals Activation of Transcription Factor Nrf-2 and Its Downstream Targets in Response to Moloney Murine Leukemia Virus ts1-Induced Thiol Depletion and Oxidative Stress in Astrocytes

2004 ◽  
Vol 78 (21) ◽  
pp. 11926-11938 ◽  
Author(s):  
Wenan Qiang ◽  
Jodi M. Cahill ◽  
Jinrong Liu ◽  
Xianghong Kuang ◽  
Na Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Transcription Factor ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Moloney Murine Leukemia Virus ◽  
Ros Accumulation ◽  
And Oxidative Stress ◽  
Murine Leukemia

ABSTRACT The neuroimmunodegenerative syndrome that develops in mice infected with ts1, a mutant of Moloney murine leukemia virus, resembles human AIDS. Both ts1 and human immunodeficiency virus type 1 infect astrocytes, microglia, and oligodendrocytes but do not infect neurons. Oxidative stress has been implicated in the neuropathology of AIDS dementia and other neurodegenerative diseases. We report here that ts1 infection of astrocytes (both transformed C1 cells and primary cultures) also induces thiol (i.e., glutathione and cysteine) depletion and reactive oxygen species (ROS) accumulation, events occurring in parallel with viral envelope precursor gPr80 env accumulation and upregulated expression of endoplasmic reticulum chaperones GRP78 and GRP94. Furthermore, ts1-infected astrocytes mobilize their thiol redox defenses by upregulating levels of the Nrf-2 transcription factor, as well its targets, the xCT cystine/glutamate antiporter, γ-glutamylcysteine ligase, and glutathione peroxidase. Depleting intracellular thiols by treating uninfected astrocytes with buthionine sulfoximine (BSO), a glutathione synthesis inhibitor, or by culturing in cystine-deficient medium, also induces ROS accumulation, activates Nrf-2, and upregulates Nrf-2 target gene expression in these astrocytes. Overexpression of Nrf-2 in astrocytes specifically increases expression of the above thiol synthesis-related proteins. Further treatment with BSO or N-acetylcysteine in transfected cells modulates this expression. Thiol depletion also accelerates cell death, while thiol supplementation promotes survival of ts1-infected cells. Together, our results indicate that ts1 infection of astrocytes, along with ts1-induced gPr80 env accumulation, endoplasmic reticulum stress, thiol depletion, and oxidative stress, accelerates cell death; in response to the thiol depletion and oxidative stress, astrocytes activate their Nrf-2-mediated thiol antioxidant defenses, promoting cell survival.

scholarly journals SETD1A augments sorafenib primary resistance via activating YAP in hepatocellular carcinoma

2020 ◽  
Author(s):  
jugang wu ◽  
Feng Li ◽  
Yan Xia ◽  
Hongjuan Chai ◽  
Yan Gu
Keyword(s):  
Cell Death ◽  
Survival Rate ◽  
Cell Lines ◽  
Cell Counting ◽  
Blue Staining ◽  
Mrna Levels ◽  
Primary Resistance ◽  
Lower Survival Rate ◽  
Histone Lysine Methyltransferase ◽  
Treatment Agent

Abstract Background: Sorafenib, the approved first-line chemotherapy drug for HCC, remains the key treatment agent which can effectively improve the survival rate of advanced HCC patients. However, the sorafenib primary resistance limits the application of sorafenib for HCC treatment. The aims of current study are to explore the role and mechanism of SETD1A (Histone Lysine Methyltransferase SET Domain Containing 1A) in sorafenib primary resistance. Methods: The expression of SETD1A in HCC was analyzed by Gene Expression Profiling Interactive Analysis. The survival of HCC patients was analyzed by KM plotter: Kaplan-Meier Plotter. Western Blot and Real-time qPCR were performed to measure the protein and mRNA levels, respectively. Cell counting kit-8 assay and colony formation assay were performed to determine cell viability and proliferation. Propidium Iodide and Trypan Blue staining assays were performed to investigate cell death. Results: Here, we showed that the expression of SETD1A was markedly upregulated in both HCC cell lines and tumor tissues compared to normal hepatocytes and corresponding non-tumor liver tissues, respectively. The patients who had higher level of SETD1A underwent lower survival rate of overall and sorafenib treated HCC patients, respectively. In addition, SETD1A expression was positively correlated with the IC 50 of sorafenib treated HCC cell lines. Furthermore, we indicated that knockdown of SETD1 augmented proliferation inhibition and cell death induced by sorafenib. SETD1A deficiency impaired YAP phosphorylation and activation. Conclusions: Taken together, the current study demonstrated that STED1A enhanced YAP activation to induce sorafenib primary resistance in HCC.

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