scholarly journals p53 Initiates Apoptosis by Transcriptionally Targeting the Antiapoptotic Protein ARC

2007 ◽  
Vol 28 (2) ◽  
pp. 564-574 ◽  
Author(s):  
Yu-Zhen Li ◽  
Dao-Yuan Lu ◽  
Wei-Qi Tan ◽  
Jian-Xun Wang ◽  
Pei-Feng Li
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Apoptotic Pathway ◽  
P53 Expression ◽  
Antiapoptotic Protein ◽  
N Terminus ◽  
P53 Activation

ABSTRACT p53 plays an important role in regulating apoptosis. However, the molecular mechanism by which it initiates the apoptotic program still remains to be fully understood. Here, we report that p53 can transcriptionally target the antiapoptotic protein, apoptosis repressor with caspase recruitment domain (ARC). Our results show that reactive oxygen species and anoxia lead to the up-regulation of p53 expression. Concomitantly, ARC is down-regulated at both the protein and mRNA levels. Knockdown of p53 expression can attenuate the decreases in ARC protein and mRNA levels, indicating that ARC down-regulation is a consequence of p53 activation. Strikingly, p53-induced ARC repression occurs in a transcription-dependent manner. We further demonstrate that the p53 up-regulated modulator of apoptosis (PUMA) and Bad are up-regulated in response to the stimulation with reactive oxygen species or anoxia, and p53 is responsible for their up-regulation. ARC can interact with PUMA or Bad via its N terminus. Such an interaction displaces the association of PUMA or Bad with Bcl-2. ARC repression by p53 leads to its failure to counteract the proapoptotic activity of PUMA and Bad. Thus, our data reveal a novel p53 apoptotic pathway in which it initiates apoptosis by transcriptionally repressing ARC.

Reactive oxygen species and mitochondrial membrane potential are modulated during CDDP-induced apoptosis in EC-109 cellsThis paper is one of a selection of papers in this Special Issue, entitled International Symposium on Recent Advances in Molecular, Clinical, and Social Medicine, and has undergone the Journal's usual peer-review process.

2007 ◽  
Vol 85 (2) ◽  
pp. 265-271 ◽  
Author(s):  
Xu-Bin Jing ◽  
Xian-Bin Cai ◽  
Hui Hu ◽  
Su-Zuan Chen ◽  
Bin-Ming Chen ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Peer Review Process ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Apoptotic Pathway ◽  
Highly Active ◽  
Inhibition Of Growth ◽  
Induced Apoptosis ◽  
Dose Dependent

cis-Diamminedichloroplatinum (CDDP), commonly know as cisplatin, is a well known DNA-damaging agent, which is highly active in suppressing the proliferation of tumor cells. However, it is not clear that CDDP can induce growth inhibition of esophagus cancer cells. Using the cell line EC-109 from the esophagus, we found that CDDP would induce apoptotic responses. The addition of CDDP to cells led to the inhibition of growth in a time- and dose-dependent manner. CDDP generated reactive oxygen species (ROSs) in cells, which brought about a reduction in the intracellular mitochondrial transmembrane potential (Δψm), leading to apoptosis. Our findings demonstrate that ROSs, and the resulting oxidative stress, play a pivotal role in apoptosis. Preincubation of EC-109 cells with the hydrogen-peroxide-scavenging enzyme catalase partially inhibited the following: (i) the production of ROS; (ii) the disruption of the Δψm; and (iii) apoptosis. These results indicate that the enhancement of the generation of ROS and the disruption of Δψm are events involved in the apoptotic pathway of EC-109 induced by CDDP.

Reactive oxygen species modulate HIF-1 mediated PAI-1 expression: involvement of the GTPase Rac1

2003 ◽  
Vol 89 (05) ◽  
pp. 926-935 ◽  
Author(s):  
Utta Berchner-Pfannschmidt ◽  
Christoph Wotzlaw ◽  
Robbert Cool ◽  
Joachim Fandrey ◽  
Helmut Acker ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Plasminogen Activator Inhibitor ◽  
Dominant Negative ◽  
Mrna Levels ◽  
Ros Production ◽  
Oxygen Species ◽  
Plasminogen Activator Inhibitor 1 ◽  
Pai 1

SummaryThe hypoxia-inducible transcription factor HIF-1 mediates upregulation of plasminogen activator inhibitor-1 (PAI-1) expression under hypoxia. Reactive oxygen species (ROS) have also been implicated in PAI-1 gene expression. However, the role of ROS in HIF-1-mediated regulation of PAI-1 is not clear. We therefore investigated the role of the GTPase Rac1 which modulates ROS production in the pathway leading to HIF-1 and PAI-1 induction.Overexpression of constitutively activated (RacG12V) or dominant-negative (RacT17N) Rac1 increased or decreased, respectively, ROS production. In RacG12V-expressing cells, PAI-1 mRNA levels as well as HIF-1α nuclear presence were reduced under normoxia and hypoxia whereas expression of RacT17N resulted in opposite effects. Treatment with the antioxidant pyrrolidinedithiocarbamate or coexpression of the redox factor-1 restored HIF-1 and PAI-1 promoter activity in RacG12V-cells. In contrast, NFκB activation was enhanced in RacG12V-cells, but abolished by RacT17N. Thus, these findings suggest a mechanism explaining modified fibrinolysis and tissue remodeling in an oxidized environment.

scholarly journals PAC1 regulates receptor tyrosine kinase transactivation in a reactive oxygen species-dependent manner

Peptides ◽  
2019 ◽  
Vol 120 ◽  
pp. 170017
Author(s):  
Terry W. Moody ◽  
Lingaku Lee ◽  
Tatiana Iordanskaia ◽  
Irene Ramos-Alvarez ◽  
Paola Moreno ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Oxygen Species

scholarly journals Blockage of Potassium Channel Inhibits Proliferation of Glioma Cells Via Increasing Reactive Oxygen Species

2014 ◽  
Vol 22 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Li Hu ◽  
Li-Li Li ◽  
Zhi-Guo Lin ◽  
Zhi-Chao Jiang ◽  
Hong-Xing Li ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Brain Glioma ◽  
Protein Levels ◽  
Glioma Cell Proliferation

The potassium (K+) channel plays an important role in the cell cycle and proliferation of tumor cells, while its role in brain glioma cells and the signaling pathways remains unclear. We used tetraethylammonium (TEA), a nonselective antagonist of big conductance K+ channels, to block K+ channels in glioma cells, and antioxidant N-acetyl-l-cysteine (NAC) to inhibit production of intracellular reactive oxygen species (ROS). TEA showed an antiproliferation effect on C6 and U87 glioma cells in a time-dependent manner, which was accompanied by an increased intracellular ROS level. Antioxidant NAC pretreatment reversed TEA-mediated antiproliferation and restored ROS level. TEA treatment also caused significant increases in mRNA and protein levels of tumor-suppressor proteins p53 and p21, and the upregulation was attenuated by pretreatment of NAC. Our results suggest that K+ channel activity significantly contributes to brain glioma cell proliferation via increasing ROS, and it might be an upstream factor triggering the activation of the p53/p21Cip1-dependent signaling pathway, consequently leading to glioma cell cycle arrest.

scholarly journals Ethyl Rosmarinate Protects High Glucose-Induced Injury in Human Endothelial Cells

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3372 ◽  
Author(s):  
Yan-Hui Shen ◽  
Li-Ying Wang ◽  
Bao-Bao Zhang ◽  
Qi-Ming Hu ◽  
Pu Wang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Protective Effect ◽  
High Glucose ◽  
Reactive Oxygen ◽  
Annexin V ◽  
Ros Generation ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Jnk Pathway

Ethyl rosmarinate (RAE) is one of the active constituents from Clinopodium chinense (Benth.) O. Kuntze, which is used for diabetic treatment in Chinese folk medicine. In this study, we investigated the protective effect of RAE on high glucose-induced injury in endothelial cells and explored its underlying mechanisms. Our results showed that both RAE and rosmarinic acid (RA) increased cell viability, decreased the production of reactive oxygen species (ROS), and attenuated high glucose-induced endothelial cells apoptosis in a dose-dependent manner, as evidenced by Hochest staining, Annexin V–FITC/PI double staining, and caspase-3 activity. RAE and RA both elevated Bcl-2 expression and reduced Bax expression, according to Western blot. We also found that LY294002 (phosphatidylinositol 3-kinase, or PI3K inhibitor) weakened the protective effect of RAE. In addition, PDTC (nuclear factor-κB, or NF-κB inhibitor) and SP600125 (c-Jun N-terminal kinase, or JNK inhibitor) could inhibit the apoptosis in endothelial cells caused by high glucose. Further, we demonstrated that RAE activated Akt, and the molecular docking analysis predicted that RAE showed more affinity with Akt than RA. Moreover, we found that RAE inhibited the activation of NF-κB and JNK. These results suggested that RAE protected endothelial cells from high glucose-induced apoptosis by alleviating reactive oxygen species (ROS) generation, and regulating the PI3K/Akt/Bcl-2 pathway, the NF-κB pathway, and the JNK pathway. In general, RAE showed greater potency than RA equivalent.

scholarly journals Drosophila hemocytes recognize lymph gland tumors of mxc mutants and activate the Toll pathway in reactive oxygen species-dependent manner

2021 ◽  
Author(s):  
Suzuko Kinoshita ◽  
Kazuki Takarada ◽  
Yoshihiro H. Inoue
Keyword(s):  
Reactive Oxygen Species ◽  
Fat Body ◽  
Ectopic Expression ◽  
Reactive Oxygen ◽  
Underlying Mechanism ◽  
Innate Immune ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Matrix Metalloproteinase 1 ◽  
Membrane Components

Mechanisms of cancer cell recognition and elimination by the innate immune system remains unclear. Circulating hemocytes are associated with the hematopoietic tumors in Drosophila mxcmbn1 mutant larvae. The innate immune signalling pathways are activated in the fat body to suppress the tumor growth by inducing antimicrobial peptides (AMP). Here, we investigated the regulatory mechanism underlying the activation in the mutant. Reactive oxygen species accumulated in the hemocytes due to induction of dual oxidase and its activator. The hemocytes were also localized on the fat body. These were essential for transmitting the information on tumors toward the fat body to induce AMP expression. Regarding to the tumor recognition, we found that matrix metalloproteinase 1 (MMP1) and MMP2 were highly expressed in the tumors. Ectopic expression of MMP2 was associated with AMP induction in the mutants. Furthermore, the basement membrane components in the tumors were reduced and ultimately lost. The hemocytes may recognize the disassembly in the tumors. Our findings highlight the underlying mechanism via which macrophage-like hemocytes recognize tumor cells and relay the information toward the fat body to induce AMPs. and contribute to uncover the immune system's roles against cancer.

The molecular mechanisms of Phytophthora infestans in response to reactive oxygen species (ROS) stress

2021 ◽  
Author(s):  
Xiumei Luo ◽  
Tingting Tian ◽  
Maxime Bonnave ◽  
Xue Tan ◽  
Xiaoqing Huang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Late Blight ◽  
Phytophthora Infestans ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Microbial Pathogens ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Tor Signaling ◽  
Potato Resistance

Reactive oxygen species (ROS) are critical for the growth, development, proliferation, and pathogenicity of microbial pathogens; however, excessive levels of ROS are toxic. Little is known regarding the signaling cascades in response to ROS stress in oomycetes such as Phytophthora infestans, the causal agent of potato late blight. Here, P. infestans was used as a model system to investigate the mechanism underlying the response to ROS stress in oomycete pathogens. Results showed severe defects in sporangium germination, mycelial growth, appressorium formation, and virulence of P. infestans in response to H2O2 stress. Importantly, these phenotypes mimic those of P. infestans treated with rapamycin, the inhibitor of target of rapamycin (TOR, 1-phosphatidylinositol-3-kinase). Strong synergism occurred when P. infestans was treated with a combination of H2O2 and rapamycin, suggesting that a crosstalk exists between ROS stress and the TOR signaling pathway. Comprehensive analysis of transcriptome, proteome and phosphorylation omics showed that H2O2 stress significantly induced the operation of the TOR-mediated autophagy pathway. Monodansylcadaverine (MDC) staining showed that in the presence of H2O2 and rapamycin, the autophagosome level increased in a dosage-dependent manner. Furthermore, transgenic potatoes containing double-stranded RNA of PiTOR (TOR in P. infestans) displayed high resistance to P. infestans. Taken together, TOR is involved in the ROS response and is a potential target for control of oomycete diseases, as host-mediated silencing of PiTOR enhances potato resistance to late blight.

scholarly journals Erigeron annuus (L.) Pers. Extract Inhibits Reactive Oxygen Species (ROS) Production and Fat Accumulation in 3T3-L1 Cells by Activating an AMP-Dependent Kinase Signaling Pathway

Antioxidants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 139 ◽  
Author(s):  
Yoon-Hee Choi ◽  
Ok-Hwan Lee ◽  
Yulong Zheng ◽  
Il-Jun Kang
Keyword(s):  
Reactive Oxygen Species ◽  
Signaling Pathway ◽  
Water Extract ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Ros Production ◽  
Oxygen Species ◽  
Fat Accumulation ◽  
Ampk Signaling ◽  
Erigeron Annuus

Obesity is one of the major public health problems in the world because it is implicated in metabolic syndromes, such as type 2 diabetes, hypertension, and cardiovascular diseases. The objective of this study was to investigate whether Erigeron annuus (L.) Pers. (EAP) extract suppresses reactive oxygen species (ROS) production and fat accumulation in 3T3-L1 cells by activating an AMP-dependent kinase (AMPK) signaling pathway. Our results showed that EAP water extract significantly inhibits ROS production, adipogenesis, and lipogenesis during differentiation of 3T3-L1 preadipocytes. In addition, EAP decreased mRNA and protein levels of proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα). Moreover, EAP suppressed mRNA expressions of fatty acid synthase (FAS), lipoprotein lipase (LPL), adipocyte protein 2 (aP2) in a dose-dependent manner. Whereas, EAP upregulated adiponectin expression, phosphorylation levels of AMPK and carnitine palmitoyltransferase 1 (CPT-1) protein level during differentiation of 3T3-L1 preadipocytes. These results suggest that EAP water extract can exert ROS-linked anti-obesity effect through the mechanism that might involve inhibition of ROS production, adipogenesis and lipogenesis via an activating AMPK signaling pathway.

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