LIVIVO - Search results -

Search results

Result 1 - 10 of total 17

Search options

Article: Identification of driver and passenger DNA methylation in cancer by epigenomic analysis.

Kalari, Satish / Pfeifer, Gerd P

2010 Volume 70, Page(s) 277–308

Abstract: Human cancer genomes are characterized by widespread aberrations in DNA methylation patterns including DNA hypomethylation of mostly repetitive sequences and hypermethylation of numerous CpG islands. The analysis of DNA methylation patterns in cancer has ...

Abstract	Human cancer genomes are characterized by widespread aberrations in DNA methylation patterns including DNA hypomethylation of mostly repetitive sequences and hypermethylation of numerous CpG islands. The analysis of DNA methylation patterns in cancer has progressed from single gene studies examining potentially important candidate genes to a more global analysis where all or almost all promoter and CpG island sequences can be analyzed. We provide a brief overview of these genome-scale methylation-profiling techniques, summarize some of the information that has been obtained with these approaches, and discuss what we have learned about the specificity of methylation aberrations in cancer at a genome-wide level. The challenge is now to identify those methylation changes that are thought to be crucial for the processes of tumor initiation, tumor progression, or metastasis and distinguish these from methylation changes that are merely passenger events that accompany the transformation process but have no effect per se on the process of carcinogenesis.
MeSH term(s)	Cell Transformation, Neoplastic/genetics ; Chromatin/metabolism ; CpG Islands ; DNA Methylation ; Epigenesis, Genetic ; Female ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Genomic Instability ; Humans ; Male ; Neoplasms/genetics ; Polycomb-Group Proteins ; Repressor Proteins/metabolism ; Signal Transduction ; Wnt Proteins/metabolism
Chemical Substances	Chromatin ; Polycomb-Group Proteins ; Repressor Proteins ; Wnt Proteins
Language	English
Publishing date	2010-10-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	148-x
ISSN	0065-2660
ISSN	0065-2660
DOI	10.1016/B978-0-12-380866-0.60010-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Se 836: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article: Role of acylglycerol kinase in LPA-induced IL-8 secretion and transactivation of epidermal growth factor-receptor in human bronchial epithelial cells.

Kalari, Satish / Zhao, Yutong / Spannhake, Ernst Wm / Berdyshev, Evgeny V / Natarajan, Viswanathan

American journal of physiology. Lung cellular and molecular physiology

2008 Volume 296, Issue 3, Page(s) L328–36

Abstract: LPA (lysophosphatidic acid) is a potent bioactive phospholipid, which regulates a number of diverse cellular responses through G protein-coupled LPA receptors. Intracellular LPA is generated by the phosphorylation of monoacylglycerol by acylglycerol ... ...

Abstract	LPA (lysophosphatidic acid) is a potent bioactive phospholipid, which regulates a number of diverse cellular responses through G protein-coupled LPA receptors. Intracellular LPA is generated by the phosphorylation of monoacylglycerol by acylglycerol kinase (AGK); however, the role of intracellular LPA in signaling and cellular responses remains to be elucidated. Here, we investigated signaling pathways of IL-8 secretion mediated by AGK and intracellular LPA in human bronchial epithelial cells (HBEpCs). Expression of AGK in HBEpCs was detected by real-time PCR, and overexpressed AGK was mainly localized in mitochondria as determined by immunofluorescence and confocal microscopy. Overexpression of lentiviral AGK wild type increased intracellular LPA production ( approximately 1.8-fold), enhanced LPA-mediated IL-8 secretion, and stimulated tyrosine phosphorylation epidermal growth factor-receptor (EGF-R). Furthermore, downregulation of native AGK by AGK small interfering RNA decreased intracellular LPA levels ( approximately 2-fold) and attenuated LPA-induced p38 MAPK, JNK, and NF-kappaB activation, tyrosine phosphorylation of EGF-R, and IL-8 secretion. These results suggest that native AGK regulates LPA-mediated IL-8 secretion involving MAPKs, NF-kappaB, and transactivation of EGF-R. Thus AGK may play an important role in innate immunity and airway remodeling during inflammation.
MeSH term(s)	Base Sequence ; Bronchi/cytology ; Bronchi/drug effects ; Bronchi/physiology ; Cells, Cultured ; DNA Primers/genetics ; Epithelial Cells/drug effects ; Epithelial Cells/physiology ; ErbB Receptors/genetics ; Humans ; Interleukin-8/metabolism ; Lysophospholipids/metabolism ; Lysophospholipids/pharmacology ; MAP Kinase Signaling System/drug effects ; NF-kappa B/metabolism ; Phosphotransferases (Alcohol Group Acceptor)/genetics ; Phosphotransferases (Alcohol Group Acceptor)/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; RNA, Small Interfering/genetics ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Subcellular Fractions/enzymology ; Transcriptional Activation/drug effects ; Transfection
Chemical Substances	CXCL8 protein, human ; DNA Primers ; Interleukin-8 ; Lysophospholipids ; NF-kappa B ; RNA, Messenger ; RNA, Small Interfering ; Recombinant Proteins ; AGK protein, human (EC 2.7.1.-) ; Phosphotransferases (Alcohol Group Acceptor) (EC 2.7.1.-) ; ErbB Receptors (EC 2.7.10.1) ; lysophosphatidic acid (PG6M3969SG)
Language	English
Publishing date	2008-12-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1013184-x
ISSN	1522-1504 ; 1040-0605
ISSN (online)	1522-1504
ISSN	1040-0605
DOI	10.1152/ajplung.90431.2008
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Uc I Zs.89: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.A 2749: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Nrf2 regulates hyperoxia-induced Nox4 expression in human lung endothelium: identification of functional antioxidant response elements on the Nox4 promoter.

Pendyala, Srikanth / Moitra, Jaideep / Kalari, Satish / Kleeberger, Steven R / Zhao, Yutong / Reddy, Sekhar P / Garcia, Joe G N / Natarajan, Viswanathan

Free radical biology & medicine

2011 Volume 50, Issue 12, Page(s) 1749–1759

Abstract: Reactive oxygen species (ROS) generated by vascular endothelial and smooth muscle cells contribute to the development and progression of vascular diseases. We have recently shown that hyperoxia enhances NADPH oxidase 4 (Nox4) expression, which regulates ... ...

Abstract	Reactive oxygen species (ROS) generated by vascular endothelial and smooth muscle cells contribute to the development and progression of vascular diseases. We have recently shown that hyperoxia enhances NADPH oxidase 4 (Nox4) expression, which regulates lung endothelial cell migration and angiogenesis. Regulation of Nox4 in the vasculature is poorly understood. The objective of this study was to identify the transcriptional factor(s) involved in regulation of endothelial Nox4. We found that hyperoxia-induced Nox4 expression was markedly reduced in Nrf2(-/-) mice, compared to Nrf2(+/+) mice. Exposure of human lung microvascular endothelial cells (HLMVECs) to hyperoxia stimulated Nrf2 translocation from the cytoplasm to the nucleus and increased Nox4 expression. Knockdown of Nrf2 expression using an siRNA approach attenuated basal Nox4 expression; however, it enhanced superoxide/ROS generation under both normoxia and hyperoxia. In silico analysis revealed the presence of at least three consensus sequences for the antioxidant response element (ARE) in the promoter region of Nox4. In transient transfections, hyperoxia stimulated Nox4 promoter activity in HLMVECs, and deletion of the -438 to -458 and -619 to -636 sequences markedly reduced hyperoxia-stimulated Nox4 promoter activation. ChIP analysis revealed an enhanced recruitment of Nrf2 to the endogenous Nox4 promoter spanning these two AREs after hyperoxic insult. Collectively, these results demonstrate, for the first time, a novel role for Nrf2 in regulating hyperoxia-induced Nox4 transcription via AREs in lung endothelium.
MeSH term(s)	Animals ; Cell Movement ; Cells, Cultured ; Endothelial Cells/metabolism ; Endothelium, Vascular/metabolism ; Free Radicals/metabolism ; Humans ; Hydrogen Peroxide/metabolism ; Hyperoxia/genetics ; Lung/cytology ; Lung/metabolism ; Mice ; Mice, Knockout ; NADPH Oxidase 4 ; NADPH Oxidases/genetics ; NADPH Oxidases/metabolism ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Reactive Oxygen Species/metabolism ; Response Elements/genetics ; Superoxides/metabolism
Chemical Substances	Free Radicals ; NF-E2-Related Factor 2 ; RNA, Small Interfering ; Reactive Oxygen Species ; Superoxides (11062-77-4) ; Hydrogen Peroxide (BBX060AN9V) ; NADPH Oxidase 4 (EC 1.6.3.-) ; NADPH Oxidases (EC 1.6.3.-) ; Nox4 protein, mouse (EC 1.6.3.-)
Language	English
Publishing date	2011-03-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/j.freeradbiomed.2011.03.022
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2109: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Characterization of calcineurin-dependent response element binding protein and its involvement in copper-metallothionein gene expression in Neurospora.

Kumar, Kalari Satish / Ravi Kumar, B / Siddavattam, Dayananda / Subramanyam, Chivukula

Biochemical and biophysical research communications

2006 Volume 345, Issue 3, Page(s) 1010–1013

Abstract: In continuation of our recent observations indicating the presence of a lone calcineurin-dependent response element (CDRE) in the -3730bp upstream region of copper-induced metallothionein (CuMT) gene of Neurospora [K.S. Kumar, S. Dayananda, C. ... ...

Abstract	In continuation of our recent observations indicating the presence of a lone calcineurin-dependent response element (CDRE) in the -3730bp upstream region of copper-induced metallothionein (CuMT) gene of Neurospora [K.S. Kumar, S. Dayananda, C. Subramanyam, Copper alone, but not oxidative stress, induces copper-metallothionein gene in Neurospora crassa, FEMS Microbiol. Lett. 242 (2005) 45-50], we isolated and characterized the CDRE-binding protein. The cloned upstream region of CuMT gene was used as the template to specifically amplify CDRE element, which was immobilized on CNBr-activated Sepharose 4B for use as the affinity matrix to purify the CDRE binding protein from nuclear extracts obtained from Neurospora cultures grown in presence of copper. Two-dimensional gel electrophoresis of the affinity purified protein revealed the presence of a single 17kDa protein, which was identified and characterized by MALDI-TOF. Peptide mass finger printing of tryptic digests and analysis of the 17kDa protein matched with the regulatory beta-subunit of calcineurin (Ca(2+)-calmodulin dependent protein phosphatase). Parallel identification of nuclear localization signals in this protein by in silico analysis suggests a putative role for calcineurin in the regulation of CuMT gene expression.
MeSH term(s)	Amino Acid Sequence ; Calcineurin/metabolism ; Cell Nucleus/metabolism ; Copper/metabolism ; Electrophoresis, Gel, Two-Dimensional ; Fungal Proteins/chemistry ; Fungal Proteins/physiology ; Gene Expression Regulation, Fungal ; Metallothionein/metabolism ; Molecular Sequence Data ; Neurospora/metabolism ; Nuclear Localization Signals ; Peptides/chemistry ; Protein Binding ; Response Elements ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Chemical Substances	Fungal Proteins ; Nuclear Localization Signals ; Peptides ; copper thionein ; Copper (789U1901C5) ; Metallothionein (9038-94-2) ; Calcineurin (EC 3.1.3.16)
Language	English
Publishing date	2006-07-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	0006-291X ; 0006-291X
ISSN (online)	0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2006.05.010
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 116: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Phospholipase D-mediated activation of IQGAP1 through Rac1 regulates hyperoxia-induced p47phox translocation and reactive oxygen species generation in lung endothelial cells.

Usatyuk, Peter V / Gorshkova, Irina A / He, Donghong / Zhao, Yutong / Kalari, Satish K / Garcia, Joe G N / Natarajan, Viswanathan

The Journal of biological chemistry

2009 Volume 284, Issue 22, Page(s) 15339–15352

Abstract: Phosphatidic acid generated by the activation of phospholipase D (PLD) functions as a second messenger and plays a vital role in cell signaling. Here we demonstrate that PLD-dependent generation of phosphatidic acid is critical for Rac1/IQGAP1 signal ... ...

Abstract	Phosphatidic acid generated by the activation of phospholipase D (PLD) functions as a second messenger and plays a vital role in cell signaling. Here we demonstrate that PLD-dependent generation of phosphatidic acid is critical for Rac1/IQGAP1 signal transduction, translocation of p47(phox) to cell periphery, and ROS production. Exposure of [(32)P]orthophosphate-labeled human pulmonary artery endothelial cells (HPAECs) to hyperoxia (95% O(2) and 5% CO(2)) in the presence of 0.05% 1-butanol, but not tertiary-butanol, stimulated PLD as evidenced by accumulation of [(32)P]phosphatidylbutanol. Infection of HPAECs with adenoviral constructs of PLD1 and PLD2 wild-type potentiated hyperoxia-induced PLD activation and accumulation of O(2)(.)/reactive oxygen species (ROS). Conversely, overexpression of catalytically inactive mutants of PLD (hPLD1-K898R or mPLD2-K758R) or down-regulation of expression of PLD with PLD1 or PLD2 siRNA did not augment hyperoxia-induced [(32)P]phosphatidylbutanol accumulation and ROS generation. Hyperoxia caused rapid activation and redistribution of Rac1, and IQGAP1 to cell periphery, and down-regulation of Rac1, and IQGAP1 attenuated hyperoxia-induced tyrosine phosphorylation of Src and cortactin and ROS generation. Further, hyperoxia-mediated redistribution of Rac1, and IQGAP1 to membrane ruffles, was attenuated by PLD1 or PLD2 small interference RNA, suggesting that PLD is upstream of the Rac1/IQGAP1 signaling cascade. Finally, small interference RNA for PLD1 or PLD2 attenuated hyperoxia-induced cortactin tyrosine phosphorylation and abolished Src, cortactin, and p47(phox) redistribution to cell periphery. These results demonstrate a role of PLD in hyperoxia-mediated IQGAP1 activation through Rac1 in tyrosine phosphorylation of Src and cortactin, as well as in p47(phox) translocation and ROS formation in human lung endothelial cells.
MeSH term(s)	Biocatalysis ; Cell Membrane/enzymology ; Cortactin/metabolism ; Down-Regulation/drug effects ; Endothelial Cells/cytology ; Endothelial Cells/enzymology ; Enzyme Activation ; Guanine Nucleotide Exchange Factors/metabolism ; Humans ; Hyperoxia/enzymology ; Lung/cytology ; Mutant Proteins/metabolism ; NADPH Oxidases/metabolism ; Phospholipase D/metabolism ; Phosphotyrosine/metabolism ; Protein Binding ; Protein Transport ; RNA, Small Interfering/metabolism ; Reactive Oxygen Species/metabolism ; T-Lymphoma Invasion and Metastasis-inducing Protein 1 ; rac1 GTP-Binding Protein/metabolism ; ras GTPase-Activating Proteins/metabolism ; src-Family Kinases/metabolism
Chemical Substances	Cortactin ; Guanine Nucleotide Exchange Factors ; IQ motif containing GTPase activating protein 1 ; Mutant Proteins ; RNA, Small Interfering ; Reactive Oxygen Species ; T-Lymphoma Invasion and Metastasis-inducing Protein 1 ; TIAM1 protein, human ; ras GTPase-Activating Proteins ; Phosphotyrosine (21820-51-9) ; NADPH Oxidases (EC 1.6.3.-) ; neutrophil cytosolic factor 1 (EC 1.6.3.1) ; src-Family Kinases (EC 2.7.10.2) ; phospholipase D2 (EC 3.1.4.-) ; Phospholipase D (EC 3.1.4.4) ; phospholipase D1 (EC 3.1.4.4) ; rac1 GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2009-04-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M109.005439
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.108: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Sphingosine kinase 1 is required for mesothelioma cell proliferation: role of histone acetylation.

Kalari, Satish / Moolky, Nagabhushan / Pendyala, Srikanth / Berdyshev, Evgeny V / Rolle, Cleo / Kanteti, Rajani / Kanteti, Archana / Ma, Wenli / He, Donghong / Husain, Aliya N / Kindler, Hedy L / Kanteti, Prasad / Salgia, Ravi / Natarajan, Viswanathan

PloS one

2012 Volume 7, Issue 9, Page(s) e45330

Abstract: Background: Malignant pleural mesothelioma (MPM) is a devastating disease with an overall poor prognosis. Despite the recent advances in targeted molecular therapies, there is a clear and urgent need for the identification of novel mesothelioma targets ... ...

Abstract	Background: Malignant pleural mesothelioma (MPM) is a devastating disease with an overall poor prognosis. Despite the recent advances in targeted molecular therapies, there is a clear and urgent need for the identification of novel mesothelioma targets for the development of highly efficacious therapeutics. Methodology/principal findings: In this study, we report that the expression of Sphingosine Kinase 1 (SphK1) protein was preferentially elevated in MPM tumor tissues (49 epithelioid and 13 sarcomatoid) compared to normal tissue (n = 13). In addition, we also observed significantly elevated levels of SphK1 and SphK2 mRNA and SphK1 protein expression in MPM cell lines such as H2691, H513 and H2461 compared to the non-malignant mesothelial Met5 cells. The underlying mechanism appears to be mediated by SphK1 induced upregulation of select gene transcription programs such as that of CBP/p300 and PCAF, two histone acetyl transferases (HAT), and the down regulation of cell cycle dependent kinase inhibitor genes such as p27Kip1 and p21Cip1. In addition, using immunoprecipitates of anti-acetylated histone antibody from SphK inhibitor, SphK-I2 treated Met5A and H2691 cell lysates, we also showed activation of other cell proliferation related genes, such as Top2A (DNA replication), AKB (chromosome remodeling and mitotic spindle formation), and suppression of p21 CIP1 and p27KIP1. The CDK2, HAT1 and MYST2 were, however, unaffected in the above study. Using SphK inhibitor and specific siRNA targeting either SphK1 or SphK2, we also unequivocally established that SphK1, but not SphK2, promotes H2691 mesothelioma cell proliferation. Using a multi-walled carbon nanotubes induced peritoneal mesothelioma mouse model, we showed that the SphK1-/- null mice exhibited significantly less inflammation and granulamatous nodules compared to their wild type counterparts. Conclusions/significance: The lipid kinase SphK1 plays a positive and essential role in the growth and development of malignant mesothelioma and is therefore a likely therapeutic target.
MeSH term(s)	Acetylation ; Animals ; Cell Line ; Cell Line, Tumor ; Cell Proliferation ; Chromatin Immunoprecipitation ; Histones/metabolism ; Humans ; Immunoblotting ; Immunohistochemistry ; Male ; Mesothelioma/enzymology ; Mice ; Mice, Inbred C57BL ; Phosphotransferases (Alcohol Group Acceptor)/genetics ; Phosphotransferases (Alcohol Group Acceptor)/metabolism ; Tandem Mass Spectrometry
Chemical Substances	Histones ; Phosphotransferases (Alcohol Group Acceptor) (EC 2.7.1.-) ; sphingosine kinase (EC 2.7.1.-)
Language	English
Publishing date	2012-09-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0045330
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Novel role for non-muscle myosin light chain kinase (MLCK) in hyperoxia-induced recruitment of cytoskeletal proteins, NADPH oxidase activation, and reactive oxygen species generation in lung endothelium.

Usatyuk, Peter V / Singleton, Patrick A / Pendyala, Srikanth / Kalari, Satish K / He, Donghong / Gorshkova, Irina A / Camp, Sara M / Moitra, Jaideep / Dudek, Steven M / Garcia, Joe G N / Natarajan, Viswanathan

The Journal of biological chemistry

2012 Volume 287, Issue 12, Page(s) 9360–9375

Abstract: We recently demonstrated that hyperoxia (HO) activates lung endothelial cell NADPH oxidase and generates reactive oxygen species (ROS)/superoxide via Src-dependent tyrosine phosphorylation of p47(phox) and cortactin. Here, we demonstrate that the non- ... ...

Abstract	We recently demonstrated that hyperoxia (HO) activates lung endothelial cell NADPH oxidase and generates reactive oxygen species (ROS)/superoxide via Src-dependent tyrosine phosphorylation of p47(phox) and cortactin. Here, we demonstrate that the non-muscle ~214-kDa myosin light chain (MLC) kinase (nmMLCK) modulates the interaction between cortactin and p47(phox) that plays a role in the assembly and activation of endothelial NADPH oxidase. Overexpression of FLAG-tagged wild type MLCK in human pulmonary artery endothelial cells enhanced interaction and co-localization between cortactin and p47(phox) at the cell periphery and ROS production, whereas abrogation of MLCK using specific siRNA significantly inhibited the above. Furthermore, HO stimulated phosphorylation of MLC and recruitment of phosphorylated and non-phosphorylated cortactin, MLC, Src, and p47(phox) to caveolin-enriched microdomains (CEM), whereas silencing nmMLCK with siRNA blocked recruitment of these components to CEM and ROS generation. Exposure of nmMLCK(-/-) null mice to HO (72 h) reduced ROS production, lung inflammation, and pulmonary leak compared with control mice. These results suggest a novel role for nmMLCK in hyperoxia-induced recruitment of cytoskeletal proteins and NADPH oxidase components to CEM, ROS production, and lung injury.
MeSH term(s)	Animals ; Cells, Cultured ; Cortactin/genetics ; Cortactin/metabolism ; Endothelial Cells/cytology ; Endothelial Cells/enzymology ; Endothelial Cells/metabolism ; Enzyme Activation ; Humans ; Hyperoxia/enzymology ; Hyperoxia/genetics ; Hyperoxia/metabolism ; Lung/cytology ; Lung/enzymology ; Lung/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myosin-Light-Chain Kinase/genetics ; Myosin-Light-Chain Kinase/metabolism ; NADPH Oxidases/genetics ; NADPH Oxidases/metabolism ; Protein Binding ; Reactive Oxygen Species/metabolism
Chemical Substances	Cortactin ; Reactive Oxygen Species ; NADPH Oxidases (EC 1.6.3.-) ; neutrophil cytosolic factor 1 (EC 1.6.3.1) ; Myosin-Light-Chain Kinase (EC 2.7.11.18)
Language	English
Publishing date	2012-01-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M111.294546
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.108: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Intracellular S1P generation is essential for S1P-induced motility of human lung endothelial cells: role of sphingosine kinase 1 and S1P lyase.

Berdyshev, Evgeny V / Gorshkova, Irina / Usatyuk, Peter / Kalari, Satish / Zhao, Yutong / Pyne, Nigel J / Pyne, Susan / Sabbadini, Roger A / Garcia, Joe G N / Natarajan, Viswanathan

PloS one

2011 Volume 6, Issue 1, Page(s) e16571

Abstract: Background: Earlier we have shown that extracellular sphingosine-1-phosphate (S1P) induces migration of human pulmonary artery endothelial cells (HPAECs) through the activation of S1P(1) receptor, PKCε, and PLD2-PKCζ-Rac1 signaling cascade. As ... ...

Abstract	Background: Earlier we have shown that extracellular sphingosine-1-phosphate (S1P) induces migration of human pulmonary artery endothelial cells (HPAECs) through the activation of S1P(1) receptor, PKCε, and PLD2-PKCζ-Rac1 signaling cascade. As endothelial cells generate intracellular S1P, here we have investigated the role of sphingosine kinases (SphKs) and S1P lyase (S1PL), that regulate intracellular S1P accumulation, in HPAEC motility. Methodology/principal findings: Inhibition of SphK activity with a SphK inhibitor 2-(p-Hydroxyanilino)-4-(p-Chlorophenyl) Thiazole or down-regulation of Sphk1, but not SphK2, with siRNA decreased S1P(int), and attenuated S1P(ext) or serum-induced motility of HPAECs. On the contrary, inhibition of S1PL with 4-deoxypyridoxine or knockdown of S1PL with siRNA increased S1P(int) and potentiated motility of HPAECs to S1P(ext) or serum. S1P(ext) mediates cell motility through activation of Rac1 and IQGAP1 signal transduction in HPAECs. Silencing of SphK1 by siRNA attenuated Rac1 and IQGAP1 translocation to the cell periphery; however, knockdown of S1PL with siRNA or 4-deoxypyridoxine augmented activated Rac1 and stimulated Rac1 and IQGAP1 translocation to cell periphery. The increased cell motility mediated by down-regulation was S1PL was pertussis toxin sensitive suggesting "inside-out" signaling of intracellularly generated S1P. Although S1P did not accumulate significantly in media under basal or S1PL knockdown conditions, addition of sodium vanadate increased S1P levels in the medium and inside the cells most likely by blocking phosphatases including lipid phosphate phosphatases (LPPs). Furthermore, addition of anti-S1P mAb to the incubation medium blocked S1P(ext) or 4-deoxypyridoxine-dependent endothelial cell motility. Conclusions/significance: These results suggest S1P(ext) mediated endothelial cell motility is dependent on intracellular S1P production, which is regulated, in part, by SphK1 and S1PL.
MeSH term(s)	Aldehyde-Lyases/physiology ; Cell Movement ; Endothelial Cells/cytology ; Humans ; Lung/cytology ; Lysophospholipids/biosynthesis ; Lysophospholipids/physiology ; Phosphotransferases (Alcohol Group Acceptor)/physiology ; RNA, Small Interfering/pharmacology ; Sphingosine/analogs & derivatives ; Sphingosine/biosynthesis ; Sphingosine/physiology
Chemical Substances	Lysophospholipids ; RNA, Small Interfering ; sphingosine 1-phosphate (26993-30-6) ; Phosphotransferases (Alcohol Group Acceptor) (EC 2.7.1.-) ; sphingosine kinase (EC 2.7.1.-) ; Aldehyde-Lyases (EC 4.1.2.-) ; sphingosine 1-phosphate lyase (aldolase) (EC 4.1.2.27) ; Sphingosine (NGZ37HRE42)
Language	English
Publishing date	2011-01-31
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0016571
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Nrf2 regulates hyperoxia-induced Nox4 expression in human lung endothelium: Identification of functional antioxidant response elements on the Nox4 promoter

Pendyala, Srikanth / Moitra, Jaideep / Kalari, Satish / Kleeberger, Steven R / Zhao, Yutong / Reddy, Sekhar P / Garcia, Joe G.N / Natarajan, Viswanathan

Free radical biology & medicine. 2011 June 15, v. 50, no. 12

2011

Abstract	Reactive oxygen species (ROS) generated by vascular endothelial and smooth muscle cells contribute to the development and progression of vascular diseases. We have recently shown that hyperoxia enhances NADPH oxidase 4 (Nox4) expression, which regulates lung endothelial cell migration and angiogenesis. Regulation of Nox4 in the vasculature is poorly understood. The objective of this study was to identify the transcriptional factor(s) involved in regulation of endothelial Nox4. We found that hyperoxia-induced Nox4 expression was markedly reduced in Nrf2−/− mice, compared to Nrf2+/+ mice. Exposure of human lung microvascular endothelial cells (HLMVECs) to hyperoxia stimulated Nrf2 translocation from the cytoplasm to the nucleus and increased Nox4 expression. Knockdown of Nrf2 expression using an siRNA approach attenuated basal Nox4 expression; however, it enhanced superoxide/ROS generation under both normoxia and hyperoxia. In silico analysis revealed the presence of at least three consensus sequences for the antioxidant response element (ARE) in the promoter region of Nox4. In transient transfections, hyperoxia stimulated Nox4 promoter activity in HLMVECs, and deletion of the −438 to −458 and −619 to −636 sequences markedly reduced hyperoxia-stimulated Nox4 promoter activation. ChIP analysis revealed an enhanced recruitment of Nrf2 to the endogenous Nox4 promoter spanning these two AREs after hyperoxic insult. Collectively, these results demonstrate, for the first time, a novel role for Nrf2 in regulating hyperoxia-induced Nox4 transcription via AREs in lung endothelium.
Keywords	transcription factors ; endothelium ; cell movement ; endothelial cells ; humans ; hyperoxia ; angiogenesis ; normoxia ; reactive oxygen species ; myocytes ; smooth muscle ; vascular diseases ; mice ; response elements ; cytoplasm ; promoter regions ; small interfering RNA
Language	English
Dates of publication	2011-0615
Size	p. 1749-1759.
Publishing place	Elsevier Inc.
Document type	Article
Note	2019-12-06
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/j.freeradbiomed.2011.03.022
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Cologne/Königswinter

Zs.A 2109: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Sphingosine kinase 1 is required for mesothelioma cell proliferation

Satish Kalari / Nagabhushan Moolky / Srikanth Pendyala / Evgeny V Berdyshev / Cleo Rolle / Rajani Kanteti / Archana Kanteti / Wenli Ma / Donghong He / Aliya N Husain / Hedy L Kindler / Prasad Kanteti / Ravi Salgia / Viswanathan Natarajan

PLoS ONE, Vol 7, Iss 9, p e

role of histone acetylation.

2012 Volume 45330

Abstract: Malignant pleural mesothelioma (MPM) is a devastating disease with an overall poor prognosis. Despite the recent advances in targeted molecular therapies, there is a clear and urgent need for the identification of novel mesothelioma targets for the ... ...

Abstract	Malignant pleural mesothelioma (MPM) is a devastating disease with an overall poor prognosis. Despite the recent advances in targeted molecular therapies, there is a clear and urgent need for the identification of novel mesothelioma targets for the development of highly efficacious therapeutics.In this study, we report that the expression of Sphingosine Kinase 1 (SphK1) protein was preferentially elevated in MPM tumor tissues (49 epithelioid and 13 sarcomatoid) compared to normal tissue (n = 13). In addition, we also observed significantly elevated levels of SphK1 and SphK2 mRNA and SphK1 protein expression in MPM cell lines such as H2691, H513 and H2461 compared to the non-malignant mesothelial Met5 cells. The underlying mechanism appears to be mediated by SphK1 induced upregulation of select gene transcription programs such as that of CBP/p300 and PCAF, two histone acetyl transferases (HAT), and the down regulation of cell cycle dependent kinase inhibitor genes such as p27Kip1 and p21Cip1. In addition, using immunoprecipitates of anti-acetylated histone antibody from SphK inhibitor, SphK-I2 treated Met5A and H2691 cell lysates, we also showed activation of other cell proliferation related genes, such as Top2A (DNA replication), AKB (chromosome remodeling and mitotic spindle formation), and suppression of p21 CIP1 and p27KIP1. The CDK2, HAT1 and MYST2 were, however, unaffected in the above study. Using SphK inhibitor and specific siRNA targeting either SphK1 or SphK2, we also unequivocally established that SphK1, but not SphK2, promotes H2691 mesothelioma cell proliferation. Using a multi-walled carbon nanotubes induced peritoneal mesothelioma mouse model, we showed that the SphK1-/- null mice exhibited significantly less inflammation and granulamatous nodules compared to their wild type counterparts.The lipid kinase SphK1 plays a positive and essential role in the growth and development of malignant mesothelioma and is therefore a likely therapeutic target.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED