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High glucose-induced apoptosis in human vascular endothelial cells is mediated through NF-κB and c-Jun NH2-terminal kinase pathway and prevented by PI3K/Akt/eNOS pathway

Published on Mar 1, 2006in Cellular Signalling3.39
· DOI :10.1016/j.cellsig.2005.05.009
Feng Ming Ho10
Estimated H-index: 10
,
Wan-Wan Lin44
Estimated H-index: 44
(NTU: National Taiwan University)
+ 6 AuthorsChiau S. Liau1
Estimated H-index: 1
(NTU: National Taiwan University)
Cite
Abstract
Our previous studies demonstrated that high glucose-induced apoptosis in human umbilical vein endothelial cells (HUVECs) is mediated by sequential activation of c-Jun N-terminal kinase (JNK) and caspase, and prevented by exogenous nitric oxide (NO). In this study we further elucidated the roles of the transcriptional factor NF-κB, phosphatidylinositol 3′-kinase (PI3K), Akt and endothelial nitric oxide synthase (eNOS) in the apoptosis of HUVECs induced by high glucose. The results showed that high glucose-induced apoptosis was significantly enhanced by PI3K inhibitors (wortmannin and LY294002), NOS inhibitor (NG-nitro-arginine methyl ester) and eNOS antisense oligonucleotide. In contrast, apoptosis was markedly reduced by NF-κB inhibitor (pyrrolidine dithiocarbamate, PDTC), NF-κB antisense oligonucleotide, NO donor (sodium nitroprusside, SNP), and overexpression of Akt. The high glucose-induced NF-κB activation and transient Akt phosphorylation were prevented by the presence of vitamin C. Moreover, high glucose-induced increase in eNOS expression was attenuated by PI3K inhibitors and the negative mutant of PI3K. The activity of JNK induced by high glucose was suppressed by NF-κB-specific antisense oligonucleotide. Taken together our results demonstrated that high glucose-induced HUVECs apoptosis is through NF-κB-dependent JNK activation and reactive oxygen species (ROS)-dependent Akt dephosphorylation. Activation of the ROS/PI3K/Akt/eNOS signaling pathway in early phase exerts protective effects against the induction of apoptosis by high glucose.
  • References (29)
  • Citations (184)
Cite
References29
Newest
Published on May 17, 2002in Journal of Biological Chemistry
Sophie Brouard10
Estimated H-index: 10
(BIDMC: Beth Israel Deaconess Medical Center),
Pascal O. Berberat34
Estimated H-index: 34
(BIDMC: Beth Israel Deaconess Medical Center)
+ 3 AuthorsMiguel P. Soares58
Estimated H-index: 58
(BIDMC: Beth Israel Deaconess Medical Center)
Abstract We have shown that carbon monoxide (CO) generated by heme oxygenase-1 (HO-1) protects endothelial cells (EC) from tumor necrosis α (TNF-α)-mediated apoptosis. This effect relies on the activation of p38 MAPK. We now demonstrate that HO-1/CO requires the activation of the transcription factor NF-κB to exert this anti-apoptotic effect. Our data suggest that EC have basal levels of NF-κB activity that sustain the expression of NF-κB-dependent anti-apoptotic genes required to support the an...
Published on Nov 1, 2001in Nature43.07
Guillin Tang1
Estimated H-index: 1
,
Yuzuru Minemoto5
Estimated H-index: 5
(U of C: University of Chicago)
+ 4 AuthorsAnning Lin39
Estimated H-index: 39
(U of C: University of Chicago)
The proinflammatory cytokine tumour necrosis factor-α (TNF-α) regulates immune responses, inflammation and programmed cell death (apoptosis)1,2,3,4. The ultimate fate of a cell exposed to TNF-α is determined by signal integration between its different effectors, including IκB kinase (IKK), c-Jun N-terminal protein kinase (JNK) and caspases1. Activation of caspases is required for apoptotic cell death5, whereas IKK activation inhibits apoptosis through the transcription factor NF-κB, whose target...
Published on Nov 1, 2001in Nature43.07
Smaele de E27
Estimated H-index: 27
(U of C: University of Chicago),
Francesca Zazzeroni28
Estimated H-index: 28
(U of C: University of Chicago)
+ 5 AuthorsGuido Franzoso36
Estimated H-index: 36
In addition to coordinating immune and inflammatory responses, NF-κB/Rel transcription factors control cell survival'. Normally, NF-κB dimers are sequestered in the cytoplasm by binding to inhibitory IκB proteins, and can be activated rapidly by signals that induce the sequential phosphorylation and proteolysis of IκBs 1 . Activation of NF-KB antagonizes apoptosis or programmed cell death by numerous triggers, including the ligand engagement of death receptors' such as tumour-necrosis factor (TN...
Published on May 15, 2001in Cancer Research8.38
Qian Shi15
Estimated H-index: 15
(University of Texas MD Anderson Cancer Center),
Xiangdong Le31
Estimated H-index: 31
(University of Texas MD Anderson Cancer Center)
+ 7 AuthorsKeping Xie54
Estimated H-index: 54
Vascular endothelial growth factor (VEGF) is a key angiogenic molecule that plays an important role in the growth and metastasis of many types of human cancer, including pancreatic adenocarcinoma. In this study, we explored the regulation of VEGF in human pancreatic cancer cells. Over 70% of the human pancreatic cancer cell lines studied in vitro secreted constitutively high levels of VEGF. High VEGF-secreting cells also generally expressed an elevated steady-state level of VEGF mRNA. Kinetic an...
Published on Apr 24, 2001in Circulation23.05
Emmanouil Chavakis26
Estimated H-index: 26
(Goethe University Frankfurt),
Elisabeth Dernbach14
Estimated H-index: 14
(Goethe University Frankfurt)
+ 3 AuthorsStefanie Dimmeler132
Estimated H-index: 132
(Goethe University Frankfurt)
Background—Oxidized LDL (oxLDL) inhibits endothelial cell (EC) migration. Stimulating ECs with vascular endothelial growth factor (VEGF) leads to the activation of Akt/protein kinase B, which in turn activates endothelial nitric oxide synthase (eNOS) by phosphorylation on serine 1177. VEGF-induced cell migration is dependent on the generation of nitric oxide (NO). Therefore, we investigated whether oxLDL affects EC migration by an inhibitory effect on the Akt/eNOS pathway. Methods and Results—Du...
Published on Feb 15, 2001in Nucleic Acids Research11.15
Patricia Renard23
Estimated H-index: 23
,
Isabelle Ernest5
Estimated H-index: 5
+ 4 AuthorsJosé Remacle53
Estimated H-index: 53
The transcription factor nuclear factor κB (NFκB) is a key factor in the immune response triggered by a wide variety of molecules such as inflammatory cytokines, or some bacterial and viral products. This transcription factor represents a new target for the development of anti-inflammatory molecules, but this type of research is currently hampered by the lack of a convenient and rapid screening assay for NFκB activation. Indeed, NFκB DNA-binding capacity is traditionally estimated by radioactive...
Published on Feb 1, 2001in Journal of Clinical Investigation12.28
Albert S. Baldwin82
Estimated H-index: 82
The transcription factor NF-κB is well established as a regulator of genes encoding cytokines, cytokine receptors, and cell adhesion molecules that drive immune and inflammatory responses (1). More recently, NF-κB activation has been connected with multiple aspects of oncogenesis, including the control of apoptosis, the cell cycle, differentiation, and cell migration. Additionally, activation of NF-κB in cancer cells by chemotherapy or by radiation can blunt the ability of the cancer therapy to ...
Published on Jul 1, 2000in Cell36.22
Anne M. Verhagen16
Estimated H-index: 16
(WEHI: Walter and Eliza Hall Institute of Medical Research),
Paul G. Ekert36
Estimated H-index: 36
(WEHI: Walter and Eliza Hall Institute of Medical Research)
+ 6 AuthorsDavid L. Vaux74
Estimated H-index: 74
(WEHI: Walter and Eliza Hall Institute of Medical Research)
Abstract To identify proteins that bind mammalian IAP homolog A (MIHA, also known as XIAP), we used coimmunoprecipitation and 2D immobilized pH gradient/SDS PAGE, followed by electrospray ionization tandem mass spectrometry. DIABLO (direct IAP binding protein with low pI) is a novel protein that can bind MIHA and can also interact with MIHB and MIHC and the baculoviral IAP, OpIAP. The N-terminally processed, IAP-interacting form of DIABLO is concentrated in membrane fractions in healthy cells bu...
Published on Jun 6, 2000in Circulation23.05
Feng M. Ho3
Estimated H-index: 3
(NTU: National Taiwan University),
Shing H. Liu4
Estimated H-index: 4
(NTU: National Taiwan University)
+ 2 AuthorsShoei Yn Lin-Shiau24
Estimated H-index: 24
(NTU: National Taiwan University)
Background—Diabetes mellitus causes multiple cardiovascular complications. High glucose can induce reactive oxygen species and apoptosis in endothelial cells. Little is known about the molecular mechanisms in high glucose–induced endothelial cell apoptosis. Methods and Results—We elucidated the signaling pathway of high glucose–induced apoptosis in human umbilical vein endothelial cells (HUVECs). HUVECs were treated with media containing 5.5, 19, or 33 mmol/L of glucose in the presence or absenc...
Published on Jan 7, 2000in Circulation Research15.86
Injune Kim24
Estimated H-index: 24
(CBNU: Chonbuk National University),
Hwan Gyu Kim5
Estimated H-index: 5
(CBNU: Chonbuk National University)
+ 3 AuthorsGou Young Koh27
Estimated H-index: 27
(CBNU: Chonbuk National University)
Abstract —Angiopoietin-1 (Ang1) is a strong apoptosis survival factor for endothelial cells. In this study, the receptor/second messenger signal transduction pathway for the antiapoptotic effect of Ang1 on human umbilical vein endothelial cells was examined. Pretreatment with soluble Tie2 receptor, but not Tie1 receptor, blocked the Ang1-induced antiapoptotic effect. Ang1 induced phosphorylation of Tie2 and the p85 subunit of phosphatidylinositol 3′-kinase (PI 3′-kinase) and increased PI 3′-kina...
Cited By184
Newest
Published on Feb 18, 2019in Cell & Bioscience3.35
Huaming Cao , Dongsheng Yu (Zhengzhou University)+ 4 AuthorsLiang Sheng (Xinxiang Medical University)
Background Endothelial cells (EC) are sensitive to changes in the microenvironment, including hypoxia and ischemia. Disruption of the microtubular network has been reported in cases of ischemia. However, the signaling pathways involved in hypoxia-induced microtubular disruption are unknown. The purpose of this study was to investigate the molecular mechanisms involved in hypoxia-induced microtubular disassembly in human umbilical vein endothelial cells (HUVECs).
Published on Sep 19, 2019in Cancers
Pranay Ramteke1
Estimated H-index: 1
,
Ankita Deb + 1 AuthorsManoj Kumar Bhat23
Estimated H-index: 23
Cancer and diabetes are amongst the leading causes of deaths worldwide. There is an alarming rise in cancer incidences and mortality, with approximately 18.1 million new cases and 9.6 million deaths in 2018. A major contributory but neglected factor for risk of neoplastic transformation is hyperglycemia. Epidemiologically too, lifestyle patterns resulting in high blood glucose level, with or without the role of insulin, are more often correlated with cancer risk, progression, and mortality. The ...
Published on 2019in FEBS Open Bio1.96
G. Jin1
Estimated H-index: 1
(Bengbu Medical College),
Qiong Wang (Bengbu Medical College)+ 4 AuthorsMinglong Li (SDU: Shandong University)
Published on Feb 22, 2019in Journal of Physiology and Biochemistry2.52
Azam Hosseinzadeh8
Estimated H-index: 8
(IUMS: Iran University of Medical Sciences),
Kobra Bahrampour Juybari (Semnan University)+ 1 AuthorsAli Sharifi27
Estimated H-index: 27
(IUMS: Iran University of Medical Sciences)
The high glucose concentration is able to disturb chondrocyte homeostasis and contribute to OA pathogenesis. This study was designed to investigate the protective effects of atorvastatin (ATO) on high glucose (HG)-mediated oxidative stress and mitochondrial apoptosis in C28I2 human chondrocytes. The protective effect of ATO (0.01 and 0.1 μM) on HG (75 mM)-induced oxidative stress and apoptosis was evaluated in C28I2 cells. The effects of ATO on HG-induced intracellular ROS production and lipid p...
Published on Mar 1, 2019in Phytomedicine4.18
Aysa Rezabakhsh8
Estimated H-index: 8
(Tabriz University of Medical Sciences),
Reza Rahbarghazi12
Estimated H-index: 12
(Tabriz University of Medical Sciences)
+ 3 AuthorsAlireza Garjani17
Estimated H-index: 17
(Tabriz University of Medical Sciences)
Abstract Background Quercetin, a flavonoid antioxidant, has been found to exert therapeutic effects in diabetic condition. Autophagy represents a homeostatic cellular mechanism for the turnover of unfolds proteins and damaged organelles through a lysosome-dependent degradation manner. We speculated that quercetin could protect endothelial cells against high glucose-induced damage by promoting autophagic responses. Methods HUVECs viability was evaluated by MTT method. Griess and TBARS assays were...
Nicholas L. DePace3
Estimated H-index: 3
,
Joseph Colombo3
Estimated H-index: 3
Published on Dec 19, 2018in Molecules3.06
Yan-Hui Shen , Liying Wang3
Estimated H-index: 3
+ 6 AuthorsFeihua Wu1
Estimated H-index: 1
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 en...
View next paperBiochemistry and molecular cell biology of diabetic complications