Eukaryotic cell survival mechanisms: Disease relevance and therapeutic intervention

Life Sciences ◽  
2018 ◽  
Vol 205 ◽  
pp. 73-90 ◽  
Author(s):  
Krishna Sundar Twayana ◽  
Palaniyandi Ravanan
2018 ◽  
pp. MCB.00054-18 ◽  
Author(s):  
Eunice Domínguez-Martín ◽  
Laura Ongay-Larios ◽  
Laura Kawasaki ◽  
Olivier Vincent ◽  
Gerardo Coello ◽  
...  

The Unfolded Protein Response (UPR) is an adaptive pathway that restores cellular homeostasis after endoplasmic reticulum (ER) stress. The ER-resident kinase/ribonuclease Ire1 is the only UPR sensor conserved during evolution. Autophagy, a lysosomal degradative pathway, also contributes to the recovery of cell homeostasis after ER-stress but the interplay between these two pathways is still poorly understood. We describe the Dictyostelium discoideum ER-stress response and characterize its single bonafide Ire1 orthologue, IreA. We found that tunicamycin (TN) triggers a gene-expression reprogramming that increases the protein folding capacity of the ER and alleviates ER protein load. Further, IreA is required for cell-survival after TN-induced ER-stress and is responsible for nearly 40% of the transcriptional changes induced by TN. The response of Dictyostelium cells to ER-stress involves the combined activation of an IreA-dependent gene expression program and the autophagy pathway. These two pathways are independently activated in response to ER-stress but, interestingly, autophagy requires IreA at a later stage for proper autophagosome formation. We propose that unresolved ER-stress in cells lacking IreA causes structural alterations of the ER, leading to a late-stage blockade of autophagy clearance. This unexpected functional link may critically affect eukaryotic cell survival under ER-stress.


2016 ◽  
Vol 46 ◽  
pp. 169-179 ◽  
Author(s):  
Sara Sarroca ◽  
Patricia Molina-Martínez ◽  
Cristina Aresté ◽  
Martin Etzrodt ◽  
Pablo García de Frutos ◽  
...  

Foods ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1885
Author(s):  
Claudio Molinari ◽  
Sara Ruga ◽  
Mahitab Farghali ◽  
Rebecca Galla ◽  
Rosario Fernández Godino ◽  
...  

Background: Glaucoma is currently the leading cause of irreversible blindness; it is a neuropathy characterized by structural alterations of the optic nerve, leading to visual impairments. The aim of this work is to develop a new oral formulation able to counteract the early changes connected to glaucomatous degeneration. The composition is based on gastrodin and vitamin D3 combined with vitamin C, blackcurrant, and lycopene. Methods: Cells and tissues of the retina were used to study biological mechanisms involved in glaucoma, to slow down the progression of the disease. Experiments mimicking the conditions of glaucoma were carried out to examine the etiology of retinal degeneration. Results: Our results show a significant ability to restore glaucoma-induced damage, by counteracting ROS production and promoting cell survival by inhibiting apoptosis. These effects were confirmed by the intracellular mechanism that was activated following administration of the compound, either before or after the glaucoma induction. In particular, the main results were obtained as a preventive action of glaucoma, showing a beneficial action on all selected markers, both on cells and on eyecup preparations. It is therefore possible to hypothesize both the preventive and therapeutic use of this formulation, in the presence of risk factors, and due to its ability to inhibit the apoptotic cycle and to stimulate cell survival mechanisms, respectively. Conclusion: This formulation has exhibited an active role in the prevention or restoration of glaucoma damage for the first time.


2012 ◽  
Vol 4 (12) ◽  
pp. a008771-a008771 ◽  
Author(s):  
C.-M. Hung ◽  
L. Garcia-Haro ◽  
C. A. Sparks ◽  
D. A. Guertin

2013 ◽  
Vol 230 (3) ◽  
pp. 291-297 ◽  
Author(s):  
Canan Akfirat ◽  
Xiaotun Zhang ◽  
Aviva Ventura ◽  
Dror Berel ◽  
Mary E Colangelo ◽  
...  

2005 ◽  
Vol 333 (2) ◽  
pp. 517-523 ◽  
Author(s):  
Márcio Fritzen ◽  
Miryam Paola Alvarez Flores ◽  
Cleyson Valença Reis ◽  
Ana Marisa Chudzinski-Tavassi

RSC Advances ◽  
2016 ◽  
Vol 6 (113) ◽  
pp. 112455-112467 ◽  
Author(s):  
Vikash Kumar ◽  
Mohammad Imran Siddiqi

Phosphoinositide-3-kinases (PI3Ks) are family of lipid kinases, involved in cell survival, growth and proliferation. Role of Class II PI3Ks in cancer is emerging and gaining importance for the therapeutic intervention.


Metabolites ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 821
Author(s):  
Tobias Kammann ◽  
Jessica Hoff ◽  
Ilknur Yildirim ◽  
Blerina Shkodra ◽  
Tina Müller ◽  
...  

Cholesterol is highly abundant within all human body cells and modulates critical cellular functions related to cellular plasticity, metabolism, and survival. The cholesterol-binding toxin pneumolysin represents an essential virulence factor of Streptococcus pneumoniae in establishing pneumonia and other pneumococcal infections. Thus, cholesterol scavenging of pneumolysin is a promising strategy to reduce S. pneumoniae induced lung damage. There may also be a second cholesterol-dependent mechanism whereby pneumococcal infection and the presence of pneumolysin increase hepatic sterol biosynthesis. Here we investigated a library of polymer particles varying in size and composition that allow for the cellular delivery of cholesterol and their effects on cell survival mechanisms following pneumolysin exposure. Intracellular delivery of cholesterol by nanocarriers composed of Eudragit E100–PLGA rescued pneumolysin-induced alterations of lipid homeostasis and enhanced cell survival irrespective of neutralization of pneumolysin.


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