scholarly journals Reticulon Protein-1C: A New Hope in the Treatment of Different Neuronal Diseases

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Federica Di Sano ◽  
Mauro Piacentini
Keyword(s):  
Cell Death ◽  
Membrane Proteins ◽  
Neurodegenerative Diseases ◽  
Er Stress ◽  
Calcium Homeostasis ◽  
Neurodegenerative Disorders ◽  
Cellular Functions ◽  
Promising Target ◽  
Specific Proteins ◽  
Structure And Functions

Reticulons (RTNs) are a group of membrane proteins localized on the ER and known to regulate ER structure and functions. Several studies have suggested that RTNs are involved in different important cellular functions such as changes in calcium homeostasis, ER-stress-mediated cell death, and autophagy. RTNs have been demonstrated to exert a cancer specific proapoptotic function via the interaction or the modulation of specific proteins. Reticulons have also been implicated in different signaling pathways which are at the basis of the pathogenesis of several neurodegenerative diseases. In this paper we discuss the accumulating evidence identifying RTN-1C protein as a promising target in the treatment of different pathologies such as cancer or neurodegenerative disorders.

scholarly journals STING-mediated disruption of calcium homeostasis chronically activates ER stress and primes T cell death

2019 ◽  
Vol 216 (4) ◽  
pp. 867-883 ◽  
Author(s):  
Jianjun Wu ◽  
Yu-Ju Chen ◽  
Nicole Dobbs ◽  
Tomomi Sakai ◽  
Jen Liou ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Er Stress ◽  
Lung Disease ◽  
Calcium Homeostasis ◽  
Cell Receptor ◽  
Type I ◽  
T Cell Survival

STING gain-of-function mutations cause lung disease and T cell cytopenia through unknown mechanisms. Here, we found that these mutants induce chronic activation of ER stress and unfolded protein response (UPR), leading to T cell death by apoptosis in the StingN153S/+ mouse and in human T cells. Mechanistically, STING-N154S disrupts calcium homeostasis in T cells, thus intrinsically primes T cells to become hyperresponsive to T cell receptor signaling–induced ER stress and the UPR, leading to cell death. This intrinsic priming effect is mediated through a novel region of STING that we name “the UPR motif,” which is distinct from known domains required for type I IFN signaling. Pharmacological inhibition of ER stress prevented StingN153S/+ T cell death in vivo. By crossing StingN153S/+ to the OT-1 mouse, we fully restored CD8+ T cells and drastically ameliorated STING-associated lung disease. Together, our data uncover a critical IFN-independent function of STING that regulates calcium homeostasis, ER stress, and T cell survival.

scholarly journals Betulin Protects HT-22 Hippocampal Cells against ER Stress through Induction of Heme Oxygenase-1 and Inhibition of ROS Production

2019 ◽  
Vol 14 (12) ◽  
pp. 1934578X1989668 ◽  
Author(s):  
Phil Jun Lee ◽  
Hye-Jin Park ◽  
Hee Min Yoo ◽  
Namki Cho
Keyword(s):  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Er Stress ◽  
Heme Oxygenase ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ros Generation ◽  
Heme Oxygenase 1 ◽  
Ros Scavenging ◽  
Neuroprotective Effects

A key pathologic event in neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, is endoplasmic reticulum (ER) stress-induced neuronal cell death. ER stress-induced generation of reactive oxygen species (ROS) has been implicated in neurological disease processes. Betulin is one of the major triterpenoids found in Betula platyphylla that possesses several biological properties, including cytoprotective and antioxidative effects. Therefore, we investigated whether betulin could prevent ER stress-induced neurotoxicity in HT-22 hippocampal neuronal cells. We observed that betulin reduced the thapsigargin (TG, an ER stress inducer)-induced apoptosis of HT-22 cells. Moreover, the cytoprotective effects of betulin were comparable to those of tauroursodeoxycholic acid, a potent ER stress-reducing agent. In our study, we confirmed that the ER stress-induced accumulation of ROS plays an important role in HT-22 cell death. Betulin also displayed cytoprotective effects in TG-injured HT-22 cells by reducing ROS generation; these results were comparable to those for N-acetyl-L-cysteine, a known ROS inhibitor. In addition, SnPP, a heme oxygenase-1 (HO-1) inhibitor significantly blocked the cytoprotective effects and ROS scavenging activity of betulin. Based on these results, we believe that betulin-mediated induction of HO-1 may contribute to the neuroprotective effects against ER stress in HT-22 hippocampal cells. We also found that betulin significantly inhibited the TG-induced expression of CHOP and caspase-12. These results demonstrated that betulin could serve as a potential therapeutic agent against ER stress-induced neurodegenerative diseases.

scholarly journals ER Stress Signaling and its Role in Cancer Cell Death

2021 ◽  
Vol 8 (S1-Feb) ◽  
pp. 81-86
Author(s):  
Kavitha C V ◽  
Poornima S K
Keyword(s):  
Cell Death ◽  
Er Stress ◽  
Cancer Cell ◽  
Low Oxygen ◽  
Cellular Functions ◽  
Unfolded Protein ◽  
Cancer Cell Death ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Cellular Dysfunction

The endoplasmic-reticulum (ER) stress response represents a cellular process that is provoked by a number of circumstances that disturb folding of proteins in the ER. An evolutionarily conserved adaptive mechanismhas been developed by Eukaryotic cells, termed the unfolded protein response (UPR) to clear the unfolded proteins and restore ER homeostasis. The cellular functions deteriorate, in the conditions when ER stress cannot be reversed and this sometime lead to cell death.The poor vascularization, low oxygen supply, nutrient deprivation, and acidic pH in the tumor microenvironment stimulate the ER stress. UPR has been shown to exert a significantcytoprotective part in speedily growing cancers as it helps folding of newly synthesized proteins required for the growth of the tumor.Accumulating evidence showed that ER stress-induced cellular dysfunction and cell death are the major contributors to many diseases and making the modulators of ER stress pathways potentially attractive targets for therapeutics discovery. Herein, we will briefly summarize gesticulating cascade activated upon ER stress and its role in cancer cell death.

scholarly journals Effect of Endoplasmic Reticulum Stress on Human Trophoblast Cells: Survival Triggering or Catastrophe Resulting in Death

2021 ◽  
Author(s):  
Gurur Garip ◽  
Berrin Ozdil ◽  
Duygu Calik-Kocaturk ◽  
Fatih Oltulu ◽  
Fatma Zuhal Eroglu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Calcium Homeostasis ◽  
Cell Dynamics ◽  
Human Trophoblast ◽  
Endometrial Cells ◽  
Cell Death Pathways ◽  
Stress Studies

ABSTRACTAlthough in vitro endoplasmic reticulum (ER) stress studies have been carried out using Tunicamycin in human trophoblast cell lines in recent years, the effect of calcium homeostasis impaired by the effect of Thapsigargin on cell survival - death pathways have not been clearly demonstrated.Here, the effects of ER stress and impaired calcium homeostasis on cell death pathways such as apoptosis and autophagy in 2-dimensional and 3-dimensional cell cultures were investigated using the HTR8 / SVneo cell line representing human trophoectoderm cells and the ER stressor Thapsigargin. By using Real Time PCR, gene and immunofluorescence analyzes were studied at the protein level.In this study, it has been established that the Thapsigargin creates ER stress by increasing the level of GRP78 gene and protein in 2 and 3 dimensions of human trophoectoderm cells and that cells show different characterization properties in 2 and 3 dimensions. It has been determined that while it moves in the direction of EIF2A and IRE1A mechanisms in 2 dimensions, it proceeds in the direction of EIF2A and ATF6 mechanisms in 3 dimensions and creates different responses in survival and programmed cell death mechanisms such as apoptosis and autophagy.With forthcoming studies, it is thought that the effects of Thapsigargin on the intrinsic pathway of apoptosis and the linkage of the autophagy mechanism, the examination of the survival-death pathways in the co-culture model with endometrial cells, therapeutic target molecules that will contribute to the elucidation of intracellular cell dynamics may increase the success of implantation.

scholarly journals Lysosomal dysfunction in neurodegenerative diseases

2017 ◽  
Vol 71 (1) ◽  
pp. 0-0 ◽  
Author(s):  
Klaudia Tomala ◽  
Bożena Gabryel
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Pathophysiological Mechanism ◽  
Autophagic Vacuoles ◽  
Lysosomal Dysfunction ◽  
Altered Proteins

Recent data advocate for the implication of lysosomes in the development of programmed cell death. Lysosomal dysfunction decreased the efficiency of autophagosome/lysosome fusion that leads to vacuolation of cells. Autophagic vacuoles containing damaged organelles and altered proteins are hallmarks in most neurodegenerative disorders. These aggregates consequently disrupt cellular homeostasis causing neuronal cell death due apoptosis or necrosis. Moreover calpain mediated or mutation inducted lysosomal rupture result in release of lysosomal cathepsins into the cytoplasm and inducing neuronal cell death. In this review we emphasize the pathophysiological mechanism connecting disrupting autophagy – lysosomal pathway and lysosomal dysfunction in neuronal cell death called lysosomal cell death.

Sign in / Sign up

Export Citation Format

Share Document