scholarly journals 25-Hydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell Line

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 199
Author(s):  
Jae-Seek You ◽  
HyangI Lim ◽  
Jeong-Yeon Seo ◽  
Kyeong-Rok Kang ◽  
Do Kyung Kim ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cholesterol Metabolism ◽  
Apoptotic Cell ◽  
Death Receptor ◽  
Fibroblast Cell ◽  
Mouse Fibroblast ◽  
Apoptosis Pathway ◽  
L929 Cells ◽  
Intrinsic Apoptosis Pathway ◽  
Oxide Synthase

25-hydroxycholesterol (25-HC) is an oxysterol synthesized from cholesterol by cholesterol-25-hydroxylase during cholesterol metabolism. The aim of this study was to verify whether 25-HC induces oxiapoptophagy in fibroblasts. 25-HC not only decreased the survival of L929 cells, but also increased the number of cells with condensed chromatin and altered morphology. Fluorescence-activated cell sorting results showed that there was a dose-dependent increase in the apoptotic populations of L929 cells upon treatment with 25-HC. 25-HC-induced apoptotic cell death was mediated by the death receptor-dependent extrinsic and mitochondria-dependent intrinsic apoptosis pathway, through the cascade activation of caspases including caspase-8, -9, and -3 in L929 cells. There was an increase in the levels of reactive oxygen species and inflammatory mediators such as inducible nitric oxide synthase, cyclooxygenase-2, nitric oxide, and prostaglandin E2 in L929 cells treated with 25-HC. Moreover, 25-HC caused an increase in the expression of beclin-1 and microtubule-associated protein 1A/1B-light chain 3, an autophagy biomarker, in L929 cells. There was a significant decrease in the phosphorylation of protein kinase B (Akt) in L929 cells treated with 25-HC. Taken together, 25-HC induced oxiapoptophagy through the modulation of Akt and p53 cellular signaling pathways in L929 cells.

Nitric oxide synthase expression and apoptotic cell death in brains of AIDS and AIDS dementia patients

AIDS ◽  
1999 ◽  
Vol 13 (3) ◽  
pp. 317-326 ◽  
Author(s):  
Valérie A.M. Vincent ◽  
Corline J.A. De Groot ◽  
Paul J. Lucassen ◽  
Peter Portegies ◽  
Dirk Troost ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Nitric Oxide Synthase ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Aids Dementia ◽  
Dementia Patients ◽  
Oxide Synthase

scholarly journals Aviculin Isolated from Lespedeza cuneata Induce Apoptosis in Breast Cancer Cells through Mitochondria-Mediated Caspase Activation Pathway

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1708 ◽  
Author(s):  
Dahae Lee ◽  
Yong Hoon Lee ◽  
Kwang Ho Lee ◽  
Bum Soo Lee ◽  
Akida Alishir ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Breast Cancer Cells ◽  
Apoptotic Cell ◽  
Underlying Mechanism ◽  
Intrinsic Apoptosis ◽  
Lespedeza Cuneata ◽  
Apoptosis Pathway ◽  
Intrinsic Apoptosis Pathway ◽  
Mcf 7

The global incidence of breast cancer has increased. However, there are many impediments to the development of safe and effective anticancer drugs. The aim of the present study was to evaluate the effect of aviculin isolated from Lespedeza cuneata (Dum. Cours.) G. Don. (Fabaceae) on MCF-7 human breast cancer cells and determine the underlying mechanism. Using the bioassay-guided isolation by water soluble tetrazolium salt (WST-1)-based Ez-Cytox assay, nine compounds (four lignan glycosides (1–4), three flavonoid glycosides (5–7), and two phenolic compounds (8 and 9)) were isolated from the ethyl acetate (EA) fraction of the L. cuneata methanolic extract. Of these, aviculin (2), a lignan glycoside, was the only compound that reduced metabolic activity on MCF-7 cells below 50% (IC50: 75.47 ± 2.23 μM). The underlying mechanism was analyzed using the annexin V Alexa Fluor 488 binding assay and Western blotting. Aviculin (2) was found to induce apoptotic cell death through the intrinsic apoptosis pathway, as indicated by the increased expression of initiator caspase-9, executioner caspase-7, and poly (ADP-ribose) polymerase (PARP). Aviculin (2)-induced apoptotic cell death was accompanied by an increase in the Bax/Bcl-2 ratio. These findings demonstrated that aviculin (2) could induce breast cancer cell apoptosis through the intrinsic apoptosis pathway, and it can therefore be considered an excellent candidate for herbal treatment of breast cancer.

Melatonin modulates acute cardiac muscle damage induced by carbon tetrachloride – involvement of oxidative damage, glutathione, and arginine/NO metabolism

2020 ◽  
Author(s):  
Snezana Ćirić Zdravković ◽  
Tomislav Kostic ◽  
Zoran P Marcetić ◽  
Sulovic S Ljiljana ◽  
Biserka M Nedeljković ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Carbon Tetrachloride ◽  
Fas Ligand ◽  
Cardiac Tissue ◽  
Apoptosis Pathway ◽  
Starting Point ◽  
Extrinsic Apoptosis ◽  
Glutathione Cycle ◽  
Oxide Synthase ◽  
First Time

The present study was designed to evaluate the cardioprotective effects of melatonin (a single dose of 50 mg/kg), a naturally occurring polypharmacological molecule, in Wistar rats acutely exposed to carbon tetrachloride (CCl4). This was done for the first time by tracking different biochemical parameters that reflect rat heart antioxidative/oxidative capacities, nitric oxide/arginine metabolism, and glutathione cycle. Additionally, the extrinsic apoptosis pathway-related parameters were studied. Acute exposure to CCl4 led to an increase in the studied tissue oxidant parameters (hydrogen peroxide, malondialdehyde, carbonylated protein content), as well as the activity alteration of antioxidant (catalase, superoxide dismutase and peroxidase) and glutathione metabolizing (glutathione peroxidase, S-transferase and reductase) enzymes. Furthermore, CCl4 caused a disturbance in the tissue myeloperoxidase, nitric oxide, citrulline, arginase, and inducible nitric oxide synthase content/activities and two apoptosis-related parameters, caspase-3 and FAS ligand. Melatonin as a posttreatment prevented the changes induced by CCl4 to a differing extent and, in some cases, it was so potent that it completely abolished any tissue disturbances. This study is a promising starting point for further research directed to the development of melatonin treatment in cardiac tissue-associated diseases.

scholarly journals Epilepsy and Apoptosis Pathways

2005 ◽  
Vol 25 (12) ◽  
pp. 1557-1572 ◽  
Author(s):  
David C Henshall ◽  
Roger P Simon
Keyword(s):  
Cell Death ◽  
Neuronal Death ◽  
Apoptotic Cell ◽  
Death Receptor ◽  
Apoptotic Pathway ◽  
Apoptosis Pathway ◽  
Cell Death Pathway ◽  
Pathway Function ◽  
Apoptosis Pathways ◽  
Molecular Machinery

Epilepsy is a common, chronic neurologic disorder characterized by recurrent unprovoked seizures. Experimental modeling and clinical neuroimaging of patients has shown that certain seizures are capable of causing neuronal death. Such brain injury may contribute to epileptogenesis, impairments in cognitive function or the epilepsy phenotype. Research into cell death after seizures has identified the induction of the molecular machinery of apoptosis. Here, the authors review the clinical and experimental evidence for apoptotic cell death pathway function in the wake of seizure activity. We summarize work showing intrinsic (mitochondrial) and extrinsic (death receptor) apoptotic pathway function after seizures, activation of the caspase and Bcl-2 families of cell death modulators and the acute and chronic neuropathologic impact of intervening in these molecular cascades. Finally, we describe evolving data on nonlethal roles for these proteins in neuronal restructuring and cell excitability that have implications for shaping the epilepsy phenotype. This review highlights the work to date on apoptosis pathway signaling during seizure-induced neuronal death and epileptogenesis, and speculates on how emerging roles in brain remodeling and excitability have enriched the number of therapeutic strategies for protection against seizure-damage and epileptogenesis.

scholarly journals miR-210 Regulates Apoptotic Cell Death during Cellular Hypoxia and Reoxygenation in a Diametrically Opposite Manner

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 42
Author(s):  
Gurdeep Marwarha ◽  
Øystein Røsand ◽  
Nathan Scrimgeour ◽  
Katrine Hordnes Slagsvold ◽  
Morten Andre Høydal
Keyword(s):  
Cell Death ◽  
Cellular Response ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Biological Response ◽  
Apoptotic Cell Death ◽  
Cellular Mechanisms ◽  
Apoptosis Pathway ◽  
Intrinsic Apoptosis Pathway ◽  
Opposite Manner

Apoptotic cell death of cardiomyocytes is a characteristic hallmark of ischemia–reperfusion (I/R) injury. The master hypoxamiR, microRNA-210 (miR-210), is considered the primary driver of the cellular response to hypoxic stress. However, to date, no consensus has emerged with regards to the polarity of the miR-210-elicited cellular response, as miR-210 has been shown to exacerbate as well as attenuate hypoxia-driven apoptotic cell death. Herein, in AC-16 cardiomyocytes subjected to hypoxia-reoxygenation (H-R) stress, we unravel novel facets of miR-210 biology and resolve the biological response mediated by miR-210 into the hypoxia and reoxygenation temporal components. Using transient overexpression and decoy/inhibition vectors to modulate miR-210 expression, we elucidated a Janus role miR-210 in the cellular response to H-R stress, wherein miR-210 mitigated the hypoxia-induced apoptotic cell death but exacerbated apoptotic cell death during cellular reoxygenation. We further delineated the underlying cellular mechanisms that confer this diametrically opposite effect of miR-210 on apoptotic cell death. Our exhaustive biochemical assays cogently demonstrate that miR-210 attenuates the hypoxia-driven intrinsic apoptosis pathway, while significantly augmenting the reoxygenation-induced caspase-8-mediated extrinsic apoptosis pathway. Our study is the first to unveil this Janus role of miR-210 and to substantiate the cellular mechanisms that underlie this functional duality.

scholarly journals Bacopa monnieriExtract (CDRI-08) Modulates the NMDA Receptor Subunits and nNOS-Apoptosis Axis in Cerebellum of Hepatic Encephalopathy Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Papia Mondal ◽  
Surendra Kumar Trigun
Keyword(s):  
Nitric Oxide ◽  
Hepatic Encephalopathy ◽  
Liver Failure ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Apoptosis Pathway ◽  
Nitric Oxide Level ◽  
Nmdar Activation ◽  
Oxide Synthase ◽  
The Brain

Hepatic encephalopathy (HE), characterized by impaired cerebellar functions during chronic liver failure (CLF), involves N-methyl-D-aspartate receptor (NMDAR) overactivation in the brain cells.Bacopa monnieri(BM) extract is a known neuroprotectant. The present paper evaluates whether BM extract is able to modulate the two NMDAR subunits (NR2A and NR2B) and its downstream mediators in cerebellum of rats with chronic liver failure (CLF), induced by administration of 50 mg/kg bw thioacetamide (TAA) i.p. for 14 days, and in the TAA group rats orally treated with 200 mg/kg bw BM extract from days 8 to 14. NR2A is known to impart neuroprotection and that of NR2B induces neuronal death during NMDAR activation. Neuronal nitric oxide synthase- (nNOS-) apoptosis pathway is known to mediate NMDAR led excitotoxicity. The level of NR2A was found to be significantly reduced with a concomitant increase of NR2B in cerebellum of the CLF rats. This was consistent with significantly enhanced nNOS expression, nitric oxide level, and reduced Bcl2/Bax ratio. Moreover, treatment with BM extract reversed the NR2A/NR2B ratio and also normalized the levels of nNOS-apoptotic factors in cerebellum of those rats. The findings suggest modulation of NR2A and NR2B expression by BM extract to prevent neurochemical alterations associated with HE.

hsTRAIL/Apo2L Induces Apoptosis in Enteropathy-Associated T-Cell Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1665-1665
Author(s):  
Marijn Radersma ◽  
Laura R de Baaij ◽  
Nathalie J Hijmering ◽  
Gert Ossenkoppele ◽  
Chris JLM Meijer ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Therapeutic Option ◽  
Survival Rates ◽  
Death Receptor ◽  
Isolated Cells ◽  
Lymphoma Cells ◽  
Apoptosis Pathway ◽  
Intrinsic Apoptosis Pathway ◽  
Trail Receptors ◽  
Induced Apoptosis

Abstract Abstract 1665 EATL is an intestinal tumor of aberrant intraepithelial T-lymphocytes (IELs) and may be preceded by refractory celiac disease type II (RCD II). Current therapies include surgery, chemotherapy and autologous and/or allogeneic stem cell transplantation. Despite these therapies, the overall outcome of EATL is very poor with 1- and 5-year survival rates in the range of 31–39% and 8–20%, respectively. Therefore, new therapeutic options are needed. Human soluble tumor necrosis factor-related apoptosis-inducing ligand, hsTRAIL/Apo2L, a member of the TNF family, has proven to selectively kill tumor cells via an alternative, death-receptor mediated apoptosis pathway. In this present study we evaluated if hsTRAIL/Apo2L induces apoptosis in both isolated lymphoma cells of EATL biopsies and isolated cells of RCD II biopsies. hsTRAIL/Apo2L induced apoptosis in isolated EATL lymphoma cells. RCD II cells were less sensitive to hsTRAIL/Apo2L compared to EATL cells. hsTRAIL/Apo2L induced apoptosis in EATL cells was caspase-9 dependent, but unexpectedly active caspase-8 involvement could not be detected. RT-MLPA analysis on EATL samples confirmed this observation by showing increased levels of c-Flip in EATL cells, which suggests a blockage in the extrinsic apoptosis pathway. Both EATL and RCDII cells showed expression of TRAIL receptors R1 and R2 and almost no expression of R3 and R4. In conclusion, our study showed that hsTRAIL/Apo2L induces apoptosis in EATL cells through the intrinsic apoptosis pathway. Moreover, we showed that TRAIL receptor R1 and R2 are expressed in EATL cells. Based on these results, hsTRAIL/Apo2L may be a new therapeutic option for EATL patients. Disclosures: No relevant conflicts of interest to declare.

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