scholarly journals Fisetin Protects PC12 Cells from Tunicamycin-Mediated Cell Death via Reactive Oxygen Species Scavenging and Modulation of Nrf2-Driven Gene Expression, SIRT1 and MAPK Signaling in PC12 Cells

2017 ◽  
Vol 18 (4) ◽  
pp. 852 ◽  
Author(s):  
Jui-Hung Yen ◽  
Pei-Shan Wu ◽  
Shu-Fen Chen ◽  
Ming-Jiuan Wu
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Pc12 Cells ◽  
Reactive Oxygen ◽  
Mapk Signaling ◽  
Oxygen Species

Zn2+-induced ERK activation mediated by reactive oxygen species causes cell death in differentiated PC12 cells

2001 ◽  
Vol 78 (3) ◽  
pp. 600-610 ◽  
Author(s):  
Su Ryeon Seo ◽  
Seon Ah Chong ◽  
Syng-Ill Lee ◽  
Jee Young Sung ◽  
Young Soo Ahn ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Pc12 Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Erk Activation ◽  
Differentiated Pc12 Cells

Increased efflux of glutathione conjugate in acutely diabetic cardiomyocytes

2004 ◽  
Vol 82 (10) ◽  
pp. 879-887 ◽  
Author(s):  
Sanjoy Ghosh ◽  
Simon Ting ◽  
Howard Lau ◽  
Thomas Pulinilkunnil ◽  
Ding An ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Multidrug Resistance ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Multidrug Resistance Protein ◽  
Multidrug Resistance Protein 1 ◽  
Resistance Protein

In diabetes, cell death and resultant cardiomyopathy have been linked to oxidative stress and depletion of antioxidants like glutathione (GSH). Although the de novo synthesis and recycling of GSH have been extensively studied in the chronically diabetic heart, their contribution in modulating cardiac oxidative stress in acute diabetes has been largely ignored. Additionally, the possible contribution of cellular efflux in regulating GSH levels during diabetes is unknown. We used streptozotocin to make Wistar rats acutely diabetic and after 4 days examined the different processes that regulate cardiac GSH. Reduction in myocyte GSH in diabetic rats was accompanied by increased oxidative stress, excessive reactive oxygen species, and an elevated apoptotic cell death. The effect on GSH was not associated with any change in either synthesis or recycling, as both γ-glutamylcysteine synthetase gene expression (responsible for bio syn thesis) and glutathione reductase activity (involved with GSH recycling) remained unchanged. However, gene expression of multidrug resistance protein 1, a transporter implicated in effluxing GSH during oxidative stress, was elevated. GSH conjugate efflux mediated by multidrug resistance protein 1 also increased in diabetic cardiomyocytes, an effect that was blocked using MK-571, a specific inhibitor of this transporter. As MK-571 also decreased oxidative stress in diabetic cardiomyocytes, an important role can be proposed for this transporter in GSH and reactive oxygen species homeostasis in the acutely diabetic heart. Key words: cardiomyocytes, apoptosis, multidrug resistance protein, reactive oxygen species.

scholarly journals The Regulation of Reactive Oxygen Species Production during Programmed Cell Death

1998 ◽  
Vol 141 (6) ◽  
pp. 1423-1432 ◽  
Author(s):  
Shirlee Tan ◽  
Yutaka Sagara ◽  
Yuanbin Liu ◽  
Pamela Maher ◽  
David Schubert
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Reactive Oxygen ◽  
Fold Increase ◽  
Glutamate Toxicity ◽  
Ros Production ◽  
Oxygen Species ◽  
Ht22 Cells

Reactive oxygen species (ROS) are thought to be involved in many forms of programmed cell death. The role of ROS in cell death caused by oxidative glutamate toxicity was studied in an immortalized mouse hippocampal cell line (HT22). The causal relationship between ROS production and glutathione (GSH) levels, gene expression, caspase activity, and cytosolic Ca2+ concentration was examined. An initial 5–10-fold increase in ROS after glutamate addition is temporally correlated with GSH depletion. This early increase is followed by an explosive burst of ROS production to 200–400-fold above control values. The source of this burst is the mitochondrial electron transport chain, while only 5–10% of the maximum ROS production is caused by GSH depletion. Macromolecular synthesis inhibitors as well as Ac-YVAD-cmk, an interleukin 1β–converting enzyme protease inhibitor, block the late burst of ROS production and protect HT22 cells from glutamate toxicity when added early in the death program. Inhibition of intracellular Ca2+ cycling and the influx of extracellular Ca2+ also blocks maximum ROS production and protects the cells. The conclusion is that GSH depletion is not sufficient to cause the maximal mitochondrial ROS production, and that there is an early requirement for protease activation, changes in gene expression, and a late requirement for Ca2+ mobilization.

Inducible Ablation of HSPA5 Suppresses BCR-ABL1-Driven Leukemia through Massive Accumulation of Reactive Oxygen Species.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1976-1976
Author(s):  
Mi Sook Chang ◽  
Shiuan Wey ◽  
Amy Lee ◽  
Markus Müschen
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Bone Marrow ◽  
Cell Death ◽  
Western Blot ◽  
Reactive Oxygen ◽  
Bone Marrow Microenvironment ◽  
Leukemia Cells ◽  
Oxygen Species

Abstract Abstract 1976 Poster Board I-999 HSPA5 is a member of the HSP70 family and involved in the folding of proteins including the immunoglobulin m heavy chain in the ER. Of note, the HSPA5 locus at 9q34 is closely located to the ABL1-breakpoint on der9, which arises during the t(9;22)(q34; q11) translocation. Comparing gene expression levels in normal pre-B cells and myeloid progenitors to BCR-ABL1-driven Ph+ ALL and CML, we observed that HSPA5 (GRP78; BIP) is strongly upregulated in BCR-ABL1-driven leukemia cells. For these reasons, we performed a genetic loss-of-function analysis via Cre-mediated deletion of HSPA5 and HSP90B1 to study the function of HSPA5 and its related interaction partner HSP90B1 (GRP94) in BCR-ABL1-driven Ph+ ALL and CML. Bone marrow from HSPA5fl/fl and HSP90B1fl/fl mice was incubated under B lymphoid (IL7) or myeloid (IL3, IL6, SCF) progenitor cell conditions. After cytokine priming, bone marrow cells were transformed with either p190 or p210 BCR-ABL1 to induce Ph+ ALL-like or CML-like leukemia, respectively. Subsequently, HSPA5fl/fl and HSP90B1fl/fl Ph+ ALL-like and CML-like leukemias were transduced with either Cre-GFP or a GFP empty vector control. Increase or depletion of GFP+ cells over time was taken as an indication of the functional relevance of Cre-mediated deletion of HSPA5 and HSP90B1 (confirmed by genomic PCR and Western blot). These experiments showed that Cre-mediated deletion of HSP90B1 had no significant effect on viability and proliferation of leukemia cells and the fraction of Cre-GFP+HSP90B1fl/fl leukemia cells remained stable (deletion confirmed by genomic PCR and Western blot). Interestingly, Cre-GFP+HSP90B1fl/fl leukemia cells showed a strong compensatory upregulation of HSPA5 upon deletion of HSP90B1. To search for subtle effects of HSP90B1-ablation, we studied changes of Imatinib-sensitivity and colony formation. However, deletion of HSP90B1 had no effect on Imatinib-sensitivity and the ability of leukemia cells to form colonies in methylcellulose. Conversely, Cre-mediated deletion of HSPA5 could not be compensated in Ph+ ALL-like and CML-like leukemia cells: Two days after Cre-transduction, HSPA5-deleted Ph+ ALL cells sharply declined. Cre-mediated deletion of HSPA5 in Ph+ ALL cells resulted in G0/G1 cell cycle arrest and cell death in vitro. In HSPA5fl/fl CML cells, the effect of Cre-mediated HSPA5-ablation was delayed until after day 4. Gene expression analysis showed that HSPA5-deletion resulted in strong upregulation of p21 (CDKN1A) and HSPA5-interacting proteins including ORP150, DNAJC3, HSP90B1 and non-functional HSPA5 transcripts. We next tested whether survival signals from the microenvironment can rescue leukemia cell survival upon Cre-mediated deletion of HSPA5 in vivo. For this experiment, HSPA5fl/fl Ph+ ALL cells were labeled with firefly luciferase and injected into sublethally irradiated NOD/SCID recipients in the presence (Cre-GFP+) or absence (GFP+) of HSPA5-deletion. In agreement with in vitro observations, HSPA5-deletion significantly extended the latency of leukemia (median survival day 10 vs day 19; n=8 per group; p=0.04). In contrast to in vitro studies, however, all mice injected with HSPA5-deleted Ph+ ALL showed progressive leukemia growth and ultimately succumbed to the disease. Genomic PCR confirmed complete HSPA5-deletion in all Cre-GFP-transduced leukemias (n=8). Since HSPA5-deleted Ph+ ALL cells accumulated in the bone marrow, we hypothesize that bone marrow microenvironment factors can rescue survival and proliferation of HSPA5-deficient Ph+ ALL cells. While bone marrow stroma-derived SDF1a, the natural ligand of CXCR4 expressed on Ph+ ALL cells failed to rescue HSPA5-deficient Ph+ ALL cells, we found accumulation of reactive oxygen species (ROS) as the likely cause of cell death following HSPA5-deletion in Ph+ ALL: levels of ROS following HSPA5-deletion were as high as ROS levels induced by incubation of non-deleted Ph+ ALL cells with 25 mmol/l H2O2. Given the low oxygen tension within the bone marrow compared to cell culture conditions, these findings provide a rationale why Ph+ ALL cells can survive deletion of HSPA5 within the bone marrow microenvironment (pO2 1-7%) but not under in vitro conditions (pO2 21%). Since BCR-ABL1 kinase activity results in ROS production, these findings suggest that inhibition of ROS scavengers represents a novel therapeutic approach to BCR-ABL1-driven leukemias. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Protective Effect ofScutellaria litwinowiiExtract on Serum/Glucose-Deprived Cultured PC12 Cells and Determining the Role of Reactive Oxygen Species

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Maryam Afsharzadeh ◽  
Zahra Tayarani-Najaran ◽  
Aryo Zare ◽  
Seyed Hadi Mousavi
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Pc12 Cells ◽  
Reactive Oxygen Species Production ◽  
Reactive Oxygen ◽  
Glucose Deprivation ◽  
Serum Glucose ◽  
Oxygen Species ◽  
Species Production

Considering the wide, positive reporting of the role of reactive oxygen species in ischemic brain injury, searching for antioxidant drugs within herbal remedies is logical. In this study, the protective effects ofScutellaria litwinowiiBornm. & Sint. on cell viability and reactive oxygen species production in cultured PC12 cells were investigated under serum/glucose-deprivation-induced cell death. After cells were seeded overnight, they were then deprived of serum/glucose for 24 h. Cells were treated with different concentrations ofS. litwinowiiextract (7.75–250 μg/mL). Cell viability was quantitated by MTT assay, and intracellular reactive oxygen species production was measured by flow cytometry. Serum/glucose-deprivation induced significant cell death after 24 h (P< 0.001). Treatment withS. litwinowii(7.75–250 μg/mL) reduced serum/glucose deprivation-induced cytotoxicity in PC12 cells after 24 h. A significant increase in intracellular reactive oxygen species production was seen following serum/glucose deprivation (P< 0.001).S. litwinowii(62 and 125 μg/mL,P< 0.01) treatment reversed the increased reactive oxygen species production following ischemic insult. This demonstrates thatS. litwinowiiextract protects PC12 cells against serum/glucose-deprivation-induced cell death by antioxidant mechanisms, which indicates the potential therapeutic application ofS. litwinowiiin managing cerebral ischemic and neurodegenerative disorders.

scholarly journals Endothelin-2/Vasoactive Intestinal Contractor: Regulation of Expression via Reactive Oxygen Species Induced by CoCl22, and Biological Activities Including Neurite Outgrowth in PC12 Cells

2006 ◽  
Vol 6 ◽  
pp. 176-186 ◽  
Author(s):  
Eiichi Kotake-Nara ◽  
Kaname Saida
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Biological Activities ◽  
Reactive Oxygen ◽  
Neuronal Model ◽  
Oxygen Species ◽  
Regulation Of Expression ◽  
Normal Tissues

This paper reviews the local hormone endothelin-2 (ET-2), or vasoactive intestinal contractor (VIC), a member of the vasoconstrictor ET peptide family, where ET-2 is the human orthologous peptide of the murine VIC. While ET-2/VIC gene expression has been observed in some normal tissues, ET-2 recently has been reported to act as a tumor marker and as a hypoxia-induced autocrine survival factor in tumor cells. A recently published study reported that the hypoxic mimetic agent CoCl2at 200 µM increased expression of the ET-2/VIC gene, decreased expression of the ET-1 gene, and induced intracellular reactive oxygen species (ROS) increase and neurite outgrowth in neuronal model PC12 cells. The ROS was generated by addition of CoCl2to the culture medium, and the CoCl2-induced effects were completely inhibited by the antioxidantN-acetyl cysteine. Furthermore, interleukin-6 (IL-6) gene expression was up-regulated upon the differentiation induced by CoCl2. These results suggest that expression of ET-2/VIC and ET-1 mediated by CoCl2-induced ROS may be associated with neuronal differentiation through the regulation of IL-6 expression. CoCl2acts as a pro-oxidant, as do Fe(II, III) and Cu(II). However, some biological activities have been reported for CoCl2that have not been observed for other metal salts such as FeCl3, CuSO4, and NiCl2. The characteristic actions of CoCl2may be associated with the differentiation of PC12 cells. Further elucidation of the mechanism of neurite outgrowth and regulation of ET-2/VIC expression by CoCl2may lead to the development of treatments for neuronal disorders.

Carmustine induces ERK- and JNK-dependent cell death of neuronally-differentiated PC12 cells via generation of reactive oxygen species

2011 ◽  
Vol 25 (7) ◽  
pp. 1359-1365 ◽  
Author(s):  
Jeong Mi An ◽  
Seon Sook Kim ◽  
Jin Hak Rhie ◽  
Dong Min Shin ◽  
Su Ryeon Seo ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Pc12 Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Differentiated Pc12 Cells ◽  
Dependent Cell
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