scholarly journals Subtilase cytotoxin induces a novel form of Lipocalin 2, which promotes Shiga-toxigenic Escherichia coli survival

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kinnosuke Yahiro ◽  
Kohei Ogura ◽  
Yoshiyuki Goto ◽  
Sunao Iyoda ◽  
Tatsuya Kobayashi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Host Cells ◽  
Parp Cleavage ◽  
Iron Level ◽  
Lipocalin 2 ◽  
Subtilase Cytotoxin

Abstract Shiga-toxigenic Escherichia coli (STEC) infection causes severe bloody diarrhea, renal failure, and hemolytic uremic syndrome. Recent studies showed global increases in Locus for Enterocyte Effacement (LEE)-negative STEC infection. Some LEE-negative STEC produce Subtilase cytotoxin (SubAB), which cleaves endoplasmic reticulum (ER) chaperone protein BiP, inducing ER stress and apoptotic cell death. In this study, we report that SubAB induces expression of a novel form of Lipocalin-2 (LCN2), and describe its biological activity and effects on apoptotic cell death. SubAB induced expression of a novel LCN2, which was regulated by PRKR-like endoplasmic reticulum kinase via the C/EBP homologous protein pathway. SubAB-induced novel-sized LCN2 was not secreted into the culture supernatant. Increased intracellular iron level by addition of holo-transferrin or FeCl3 suppressed SubAB-induced PARP cleavage. Normal-sized FLAG-tagged LCN2 suppressed STEC growth, but this effect was not seen in the presence of SubAB- or tunicamycin-induced unglycosylated FLAG-tagged LCN2. Our study demonstrates that SubAB-induced novel-sized LCN2 does not have anti-STEC activity, suggesting that SubAB plays a crucial role in the survival of LEE-negative STEC as well as inducing apoptosis of the host cells.

scholarly journals Ginkgo biloba Prevents Oxidative Stress-Induced Apoptosis Blocking p53 Activation in Neuroblastoma Cells

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 279 ◽  
Author(s):  
Francesco Di Meo ◽  
Rossana Cuciniello ◽  
Sabrina Margarucci ◽  
Paolo Bergamo ◽  
Orsolina Petillo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Ginkgo Biloba ◽  
Apoptotic Cell ◽  
Neuroblastoma Cells ◽  
Apoptotic Cell Death ◽  
Parp Cleavage ◽  
Egb 761 ◽  
Induced Apoptosis

Oxidative stress has been associated to neuronal cell loss in neurodegenerative diseases. Neurons are post-mitotic cells that are very sensitive to oxidative stress—especially considering their limited capacity to be replaced. Therefore, reduction of oxidative stress, and inhibiting apoptosis, will potentially prevent neurodegeneration. In this study, we investigated the neuroprotective effect of Ginkgo biloba extract (EGb 761) against H2O2 induced apoptosis in SK-N-BE neuroblastoma cells. We analysed the molecular signalling pathway involved in the apoptotic cell death. H2O2 induced an increased acetylation of p53 lysine 382, a reduction in mitochondrial membrane potential, an increased BAX/Bcl-2 ratio and consequently increased Poly (ADP-ribose) polymerase (PARP) cleavage. All these effects were blocked by EGb 761 treatment. Thus, EGb 761, acting as intracellular antioxidant, protects neuroblastoma cells against activation of p53 mediated pathway and intrinsic mitochondrial apoptosis. Our results suggest that EGb 761, protecting against oxidative-stress induced apoptotic cell death, could potentially be used as nutraceutical for the prevention and treatment of neurodegenerative diseases.

scholarly journals Involvement of mitochondria in endoplasmic reticulum stress-induced apoptotic cell death pathway triggered by the prion peptide PrP106–126

2007 ◽  
Vol 0 (0) ◽  
pp. 071108171001003-??? ◽  
Author(s):  
Elisabete Ferreiro ◽  
Rui Costa ◽  
Sueli Marques ◽  
Sandra Morais Cardoso ◽  
Catarina R. Oliveira ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Endoplasmic Reticulum Stress ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Cell Death Pathway

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

Di-O-demethylcurcumin protects SK-N-SH cells against mitochondrial and endoplasmic reticulum-mediated apoptotic cell death induced by Aβ25-35

2015 ◽  
Vol 80 ◽  
pp. 110-119 ◽  
Author(s):  
Decha Pinkaew ◽  
Chatchawan Changtam ◽  
Chainarong Tocharus ◽  
Sarinthorn Thummayot ◽  
Apichart Suksamrarn ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death

Pyridoxine Preferentially Induces Auditory Neuropathy Through Mitochondrial Dysfunction and Endoplasmic Reticulum Stress-Mediated Apoptosis

2019 ◽  
Vol 128 (6_suppl) ◽  
pp. 117S-124S ◽  
Author(s):  
Channy Park ◽  
Hyewon Lim ◽  
Sung K. Moon ◽  
Raekil Park
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Protein Expression ◽  
Er Stress ◽  
Nerve Fiber ◽  
Apoptotic Cell ◽  
Auditory Neuropathy ◽  
Parp Cleavage ◽  
Ros Generation ◽  
Ganglion Neurons

Objectives: Auditory neuropathy due to toxicity mechanism of pyridoxine has not yet been fully documented. Therefore, the present study explored a direct mechanism underlying the effects of pyridoxine on auditory neuropathy in organ of Corti (OC) explants ex vivo and cochlear neuroblast cell line, VOT-33 in vitro. Methods: Primary OC explants containing spiral ganglion neurons and cultured VOT-33 cells were treated with pyridoxine. Results: In nerve fiber of primary OC explants, pyridoxine decreased staining for NF200, a neuro-cytoskeletal protein. We also found that pyridoxine-induced VOT-33 apoptosis, as indicated by accumulation of the sub-G0/G1 fraction, caspase-3 activation, and PARP cleavage. In addition, pyridoxine induced reactive oxygen species (ROS) generation and alteration of mitochondrial membrane potential transition (MPT), including Bcl-2 family protein expression and consequently Ca2+ accumulation and changes of endoplasmic reticulum (ER) stress-related protein expression such as phospho-PERK, caspase-12, Grp78, and CHOP. Conclusion: Pyridoxine preferentially induced severe cell death on nerve fiber in primary OC explants and markedly increased apoptotic cell death via mitochondria-mediated ER stress in VOT-33 cells.

PI3 Kinase Inhibition Induces Apoptotic Cell Death in Acute Lymphoblastic Leukemia Via the Mitochondrial Pathway.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1911-1911
Author(s):  
Karin von Schwarzenberg ◽  
Marco Henkel ◽  
Dennis Conzelmann ◽  
Björn Stork ◽  
Anita Bringmann ◽  
...  
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Lymphoblastic Leukemia ◽  
Death Receptor ◽  
Pi3k Pathway ◽  
Apoptotic Cell Death ◽  
Jurkat Cells ◽  
Parp Cleavage ◽  
Caspase 9 ◽  
Pi3k Inhibition

Abstract The phosphatidylinositol 3-kinase (PI3K) pathway regulates many cellular processes that are involved in tumor progression. Aberrant activation of the PI3K pathway due to an alteration of its elements like PTEN or Akt occurs quite frequently in malignant cells. Thus, inhibition of this pathway represents a promising option for the treatment of cancer patients. The best characterized PI3K inhibitors are LY294002 and wortmannin that were shown to disrupt downstream signaling and induce apoptotic cell death in tumor cells. Acute lymphoblastic leukemia (ALL) is a malignancy mainly found in young children and elderly with constitutive activation of PI3K pathway. In our study we analyzed the effect of PI3K inhibition in cell lines deduced from ALL (Jurkat, BV173, SD1, T-2) and primary leukemic cells by incubating them with increasing concentrations of inhibitors of the PI3K signaling. We found that treatment of ALL cells with LY294002, the mTOR inhibitor rapamycin or Akt inhibitor SH5 induced apoptotic cell death that was accompanied by caspase-3 activation and PARP-cleavage and interfered with intracellular PI3K/Akt signaling as analyzed by phosphorylation and expression of mTOR or P70S6K. In line with these results apoptotic cell death could be inhibited by the pan-caspase inhibitor zVAD. In order to determine the pathway of apoptosis induction we took advantage of Jurkat cells (T-ALL) overexpressing or lacking molecules involved in apoptotic pathways such as FADD, an adaptor molecule recruited to the death receptor upon ligand binding, Caspase-8, Caspase-9 or Bcl-2, an anti-apoptotic protein that prevents the release of cytochrom c from mitochondria. PI3K inhibition by LY294002 induced apoptotic cell death in cells deficient of FADD or caspase-8 with no difference to wild type cells. In contrast, cells overexpressing Bcl2 or lacking caspase-9 were resistant to apoptotic death indicating that PI3-kinase inhibition is independent of the external death receptor signaling and is mediated via the mitochondrial pathway. These results were confirmed by analyzing PARP cleavage and caspase-3 activation in utilized leukemic cell lines. Furthermore, we found that the PI3K inhibitor LY294002 induced apoptosis in ALL cells that could be increased by the etoposide, a topoisomerase inhibitor, or TRAIL. In addition, in contrast to etoposide, treatment of ALL cells with TRAIL could overcome the resistance of ALL cells to PI3K inhibition even in caspase-9 deficient Jurkat cells. Our results provide an interesting approach in designing novel therapeutic strategies to target the PI3K pathway in ALL to overcome the resistance to cytotoxic agents.

scholarly journals Epigallocatechin-3-Gallate (EGCG) Promotes Autophagy-Dependent Survival via Influencing the Balance of mTOR-AMPK Pathways upon Endoplasmic Reticulum Stress

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Marianna Holczer ◽  
Boglárka Besze ◽  
Veronika Zámbó ◽  
Miklós Csala ◽  
Gábor Bánhegyi ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Egcg Treatment ◽  
Life And Death ◽  
Er Stress Response ◽  
Negative Effect ◽  
External Stimuli

The maintenance of cellular homeostasis is largely dependent on the ability of cells to give an adequate response to various internal and external stimuli. We have recently proposed that the life-and-death decision in endoplasmic reticulum (ER) stress response is defined by a crosstalk between autophagy, apoptosis, and mTOR-AMPK pathways, where the transient switch from autophagy-dependent survival to apoptotic cell death is controlled by GADD34. The aim of the present study was to investigate the role of epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea, in promoting autophagy-dependent survival and to verify the key role in connecting GADD34 with mTOR-AMPK pathways upon prolonged ER stress. Our findings, obtained by using HEK293T cells, revealed that EGCG treatment is able to extend cell viability by inducing autophagy. We confirmed that EGCG-induced autophagy is mTOR-dependent and PKA-independent; furthermore, it also required ULK1. We show that pretreatment of cells with EGCG diminishes the negative effect of GADD34 inhibition (by guanabenz or siGADD34 treatment) on autophagy. EGCG was able to delay apoptotic cell death by upregulating autophagy-dependent survival even in the absence of GADD34. Our data suggest a novel role for EGCG in promoting cell survival via shifting the balance of mTOR-AMPK pathways in ER stress.

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.

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