scholarly journals XDeathDB: a visualization platform for cell death molecular interactions

2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Venkat Sundar Gadepalli ◽  
Hangil Kim ◽  
Yueze Liu ◽  
Tao Han ◽  
Lijun Cheng
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Web Applications ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Mitotic Cell ◽  
Cell Death Pathway ◽  
Disease Associations ◽  
R Shiny ◽  
Novel Drug

AbstractLots of cell death initiator and effector molecules, signalling pathways and subcellular sites have been identified as key mediators in both cell death processes in cancer. The XDeathDB visualization platform provides a comprehensive cell death and their crosstalk resource for deciphering the signaling network organization of interactions among different cell death modes associated with 1461 cancer types and COVID-19, with an aim to understand the molecular mechanisms of physiological cell death in disease and facilitate systems-oriented novel drug discovery in inducing cell deaths properly. Apoptosis, autosis, efferocytosis, ferroptosis, immunogenic cell death, intrinsic apoptosis, lysosomal cell death, mitotic cell death, mitochondrial permeability transition, necroptosis, parthanatos, and pyroptosis related to 12 cell deaths and their crosstalk can be observed systematically by the platform. Big data for cell death gene-disease associations, gene-cell death pathway associations, pathway-cell death mode associations, and cell death-cell death associations is collected by literature review articles and public database from iRefIndex, STRING, BioGRID, Reactom, Pathway’s commons, DisGeNET, DrugBank, and Therapeutic Target Database (TTD). An interactive webtool, XDeathDB, is built by web applications with R-Shiny, JavaScript (JS) and Shiny Server Iso. With this platform, users can search specific interactions from vast interdependent networks that occur in the realm of cell death. A multilayer spectral graph clustering method that performs convex layer aggregation to identify crosstalk function among cell death modes for a specific cancer. 147 hallmark genes of cell death could be observed in detail in these networks. These potential druggable targets are displayed systematically and tailoring networks to visualize specified relations is available to fulfil user-specific needs. Users can access XDeathDB for free at https://pcm2019.shinyapps.io/XDeathDB/.

scholarly journals Molecular mechanisms of cell death: central implication of ATP synthase in mitochondrial permeability transition

Oncogene ◽  
2014 ◽  
Vol 34 (12) ◽  
pp. 1475-1486 ◽  
Author(s):  
M Bonora ◽  
M R Wieckowski ◽  
C Chinopoulos ◽  
O Kepp ◽  
G Kroemer ◽  
...  
Keyword(s):  
Cell Death ◽  
Atp Synthase ◽  
Molecular Mechanisms ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Mitochondrial Permeability

Role of Calcium Homeostasis in Ischemic Stroke: A Review

2021 ◽  
Vol 20 ◽  
Author(s):  
Abhilash Ludhiadch ◽  
Rashmi Sharma ◽  
Aishwarya Muriki ◽  
Anjana Munshi
Keyword(s):  
Cell Death ◽  
Ischemic Stroke ◽  
Neuronal Death ◽  
Complex Disease ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Vital Role ◽  
Calcium Accumulation ◽  
Cell Death Pathway

: Stroke is the second most common cause of death worldwide. It occurs due to the insufficient supply of oxygen-rich blood to the brain. It is a complex disease with multiple associated risk factors including smoking, alcoholism, age, sex, ethnicity, etc. Calcium ions are known to play a vital role in cell death pathways, which is a ubiquitous intracellular messenger during and immediately after an ischemic period. Disruption in normal calcium hemostasis is known to be a major initiator and activator of the ischemic cell death pathway. Under Ischemic stroke conditions, glutamate is released from the neurons and glia which further activates the N-methyl-D-aspartate (NMDA) receptor and triggers the rapid translocation of Ca2+ from extracellular to intracellular spaces in cerebral tissues and vice versa. Various studies indicated that Ca2+ could have harmful effects on neurons under acute ischemic conditions. Mitochondrial dysfunction also contributes to delayed neuronal death, and it was established decades ago that massive calcium accumulation triggers mitochondrial damage. Elevated Ca2+ levels cause mitochondria to swell and release their contents. As a result oxidative stress and mitochondrial calcium accumulation activate mitochondrial permeability transition and lead to depolarization-coupled production of reactive oxygen species. This association between calcium levels and mitochondrial death suggests that elevated calcium levels might have a role in the neurological outcome in ischemic stroke. Previous studies have also reported that elevated Ca2+ levels play a role in the determination of infarct size, outcome, and recurrence of ischemic stroke. The current review has been compiled to understand the multidimensional role of altered Ca2+ levels in the initiation and alteration of neuronal death after ischemic attack. The underlying mechanisms understood to date have also been discussed.

scholarly journals Different Roles of Mitochondria in Cell Death and Inflammation: Focusing on Mitochondrial Quality Control in Ischemic Stroke and Reperfusion

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 169
Author(s):  
Marianna Carinci ◽  
Bianca Vezzani ◽  
Simone Patergnani ◽  
Peter Ludewig ◽  
Katrin Lessmann ◽  
...  
Keyword(s):  
Cell Death ◽  
Ischemic Stroke ◽  
Molecular Mechanisms ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Brain Diseases ◽  
Cell Death Pathways ◽  
Molecular Pattern ◽  
Neuroprotective Strategies

Mitochondrial dysfunctions are among the main hallmarks of several brain diseases, including ischemic stroke. An insufficient supply of oxygen and glucose in brain cells, primarily neurons, triggers a cascade of events in which mitochondria are the leading characters. Mitochondrial calcium overload, reactive oxygen species (ROS) overproduction, mitochondrial permeability transition pore (mPTP) opening, and damage-associated molecular pattern (DAMP) release place mitochondria in the center of an intricate series of chance interactions. Depending on the degree to which mitochondria are affected, they promote different pathways, ranging from inflammatory response pathways to cell death pathways. In this review, we will explore the principal mitochondrial molecular mechanisms compromised during ischemic and reperfusion injury, and we will delineate potential neuroprotective strategies targeting mitochondrial dysfunction and mitochondrial homeostasis.

scholarly journals Erratum: Molecular mechanisms of cell death: central implication of ATP synthase in mitochondrial permeability transition

Oncogene ◽  
2015 ◽  
Vol 34 (12) ◽  
pp. 1608-1608 ◽  
Author(s):  
M Bonora ◽  
M R Wieckowsk ◽  
C Chinopoulos ◽  
O Kepp ◽  
G Kroemer ◽  
...  
Keyword(s):  
Cell Death ◽  
Atp Synthase ◽  
Molecular Mechanisms ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Mitochondrial Permeability

Benzo(a)pyrene-7,8-diol-9,10-epoxide induced p53-independent necrosis via the mitochondria-associated pathway involving Bax and Bak activation

2014 ◽  
Vol 34 (2) ◽  
pp. 179-190 ◽  
Author(s):  
W Zhang ◽  
N Liu ◽  
X Wang ◽  
X Jin ◽  
H Du ◽  
...  
Keyword(s):  
Cell Death ◽  
Cytochrome C ◽  
Molecular Mechanisms ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Necrotic Cell Death ◽  
Necrotic Cell ◽  
Cytochrome C Release

Benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE) is a highly reactive DNA damage agent and can induce cell death through both p53-independent and -dependent pathways. However, little is known about the molecular mechanisms of p53-independent pathways in BPDE-induced cell death. To understand the p53-independent mechanisms, we have now examined BPDE-induced cytotoxicity in p53-deficient baby mouse kidney (BMK) cells. The results showed that BPDE could induce Bax and Bak activation, cytochrome c release, caspases activation, and necrotic cell death in the BMK cells. Bax and Bak, two key molecules of mitochondrial permeability transition pore, were interdependently activated by BPDE, with Bax and Bak translocation to and Bax/Bak homo-oligomerization in mitochondria, release of cytochrome c was induced. Importantly, cytochrome c release and necrotic cell death were diminished in BMK cells (Bax−/−), BMK cells (Bak−/−), and BMK cells (Bax−/−/Bak−/−). Furthermore, overexpression of Bcl-2 could ameliorate BPDE-induced cytochrome c release and necrosis. Together the findings suggested that BPDE-induced necrosis was modulated by the p53-independent pathway, which was related to the translocation of Bax and Bak to mitochondria, release of cytochrome c, and activation of caspases.

scholarly journals Metformin induces apoptosis via uterus mitochondrial permeability transition pore opening and protects against estradiol benzoate-induced uterine defect and associated pathophysiological disorder in female Wistar rats

2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Adeola Oluwakemi Olowofolahan ◽  
Obinna Matthew Paulinus ◽  
Heritage Mojisola Dare ◽  
Olufunso Olabode Olorunsogo
Keyword(s):  
Cell Death ◽  
Cytochrome C ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Estradiol Benzoate ◽  
Histological Evaluation ◽  
Mitochondrial Atpase ◽  
Rat Uterus ◽  
Mitochondrial Permeability ◽  
Pore Opening

Abstract Background Some antitumor or anticancer agents have been shown to execute cell death by induction of mitochondrial permeability transition (mPT) pore opening in order to elicit their chemotherapeutic effect. Therefore, this study investigated the effect of metformin on cell death via rat uterus mPT pore and estradiol benzoate-induced uterine defect and associated pathophysiological disorder in female rat. Mitochondria were isolated using differential centrifugation. The mPT pore opening, cytochrome c release and mitochondrial ATPase activity were determined spectrophotometrically. Caspases 9 and 3 activities, MDA and estradiol levels and SOD, GSH activities, were determined using ELISA technique. Histological and histochemical assessments of the uterine section were carried out using standard methods. Results Metformin at concentrations 10–90 μg/mL, showed no significant effect on mPT pore opening, mATPase activity and release of cytochrome c. However, oral administration of metformin caused mPT pore opening, enhancement of mATPase activity and activation of caspases 9 and 3 significantly at 300 and 400 mg/kg. Metformin protected against estradiol benzoate (EB)-induced uterine defect and other associated pathophysiological disorder. It also improved the antioxidant defense system. The histological evaluation revealed the protective effect of metformin on the cellular architecture of the uterus while the histochemical examination showed severe hyperplasia in the uterine section of EB-treated rats, remarkably reversed by metformin co-treatment. Conclusion This study suggests that metformin at high doses induces apoptosis via rat uterus mPT pore opening and protects against EB-induced uterine defect (hyperplasia) and associated pathophysiological disorder.

scholarly journals Mitochondria and Pharmacologic Cardiac Conditioning—At the Heart of Ischemic Injury

2021 ◽  
Vol 22 (6) ◽  
pp. 3224
Author(s):  
Christopher Lotz ◽  
Johannes Herrmann ◽  
Quirin Notz ◽  
Patrick Meybohm ◽  
Franz Kehl
Keyword(s):  
Cell Death ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Research Field ◽  
Calcium Handling ◽  
Control Mechanisms ◽  
Intrinsic Resistance ◽  
Atp Production ◽  
Cardiac Conditioning ◽  
A Cell

Pharmacologic cardiac conditioning increases the intrinsic resistance against ischemia and reperfusion (I/R) injury. The cardiac conditioning response is mediated via complex signaling networks. These networks have been an intriguing research field for decades, largely advancing our knowledge on cardiac signaling beyond the conditioning response. The centerpieces of this system are the mitochondria, a dynamic organelle, almost acting as a cell within the cell. Mitochondria comprise a plethora of functions at the crossroads of cell death or survival. These include the maintenance of aerobic ATP production and redox signaling, closely entwined with mitochondrial calcium handling and mitochondrial permeability transition. Moreover, mitochondria host pathways of programmed cell death impact the inflammatory response and contain their own mechanisms of fusion and fission (division). These act as quality control mechanisms in cellular ageing, release of pro-apoptotic factors and mitophagy. Furthermore, recently identified mechanisms of mitochondrial regeneration can increase the capacity for oxidative phosphorylation, decrease oxidative stress and might help to beneficially impact myocardial remodeling, as well as invigorate the heart against subsequent ischemic insults. The current review highlights different pathways and unresolved questions surrounding mitochondria in myocardial I/R injury and pharmacological cardiac conditioning.

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