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Article ; Online: Hepatocytes coordinate immune evasion in cancer via release of serum amyloid A proteins.

Stone, Meredith L / Lee, Jesse / Lee, Jae W / Coho, Heather / Tariveranmoshabad, Mito / Wattenberg, Max M / Choi, Hana / Herrera, Veronica M / Xue, Yuqing / Choi-Bose, Shaanti / Zingone, Sofia K / Patel, Dhruv / Markowitz, Kelly / Delman, Devora / Balachandran, Vinod P / Beatty, Gregory L

Nature immunology

2024

Abstract: T cell infiltration into tumors is a favorable prognostic feature, but most solid tumors lack productive T cell responses. Mechanisms that coordinate T cell exclusion are incompletely understood. Here we identify hepatocyte activation via interleukin-6/ ... ...

Abstract	T cell infiltration into tumors is a favorable prognostic feature, but most solid tumors lack productive T cell responses. Mechanisms that coordinate T cell exclusion are incompletely understood. Here we identify hepatocyte activation via interleukin-6/STAT3 and secretion of serum amyloid A (SAA) proteins 1 and 2 as important regulators of T cell surveillance of extrahepatic tumors. Loss of STAT3 in hepatocytes or SAA remodeled the tumor microenvironment with infiltration by CD8
Language	English
Publishing date	2024-04-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-024-01820-1
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Zs.A 5294: 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)
Zs.MG 42: Show issues

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Article ; Online: The ORMDL/Orm-serine palmitoyltransferase (SPT) complex is directly regulated by ceramide: Reconstitution of SPT regulation in isolated membranes.

Davis, Deanna L / Gable, Kenneth / Suemitsu, John / Dunn, Teresa M / Wattenberg, Binks W

The Journal of biological chemistry

2019 Volume 294, Issue 13, Page(s) 5146–5156

Abstract: Sphingolipids compose a lipid family critical for membrane structure as well as intra- and intercellular signaling. ...

Abstract	Sphingolipids compose a lipid family critical for membrane structure as well as intra- and intercellular signaling.
MeSH term(s)	Adenosine Triphosphate/metabolism ; Cell Membrane/metabolism ; Ceramides/metabolism ; Cytosol/metabolism ; Endoplasmic Reticulum/metabolism ; HeLa Cells ; Humans ; Lipid Metabolism ; Membrane Proteins/metabolism ; Serine C-Palmitoyltransferase/metabolism ; Sphingolipids/metabolism
Chemical Substances	Ceramides ; Membrane Proteins ; ORMDL3 protein, human ; Sphingolipids ; Adenosine Triphosphate (8L70Q75FXE) ; SPTLC1 protein, human (EC 2.3.1.50) ; Serine C-Palmitoyltransferase (EC 2.3.1.50)
Language	English
Publishing date	2019-01-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.RA118.007291
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Article ; Online: Mammalian ORMDL proteins mediate the feedback response in ceramide biosynthesis.

Siow, Deanna L / Wattenberg, Binks W

The Journal of biological chemistry

2012 Volume 287, Issue 48, Page(s) 40198–40204

Abstract: Background: The yeast Orm1/2 proteins regulate ceramide biosynthesis.: Results: Depletion of the mammalian Orm1/2 homologues, ORMDL1-3, eliminates the negative feedback of exogenous ceramide on ceramide biosynthesis in HeLa cells.: Conclusion: ... ...

Abstract	Background: The yeast Orm1/2 proteins regulate ceramide biosynthesis. Results: Depletion of the mammalian Orm1/2 homologues, ORMDL1-3, eliminates the negative feedback of exogenous ceramide on ceramide biosynthesis in HeLa cells. Conclusion: ORMDL proteins are the primary regulators of ceramide biosynthesis in mammalian cells. Significance: Therapeutically manipulating levels of the pro-death lipid, ceramide, requires a molecular understanding of its regulation. The mammalian ORMDL proteins are orthologues of the yeast Orm proteins (Orm1/2), which are regulators of ceramide biosynthesis. In mammalian cells, ceramide is a proapoptotic signaling sphingolipid, but it is also an obligate precursor to essential higher order sphingolipids. Therefore levels of ceramide are expected to be tightly controlled. We tested the three ORMDL isoforms for their role in homeostatically regulating ceramide biosynthesis in mammalian cells. Treatment of cells with a short chain (C6) ceramide or sphingosine resulted in a dramatic inhibition of ceramide biosynthesis. This inhibition was almost completely eliminated by ORMDL knockdown. This establishes that the ORMDL proteins mediate the feedback regulation of ceramide biosynthesis in mammalian cells. The ORMDL proteins are functionally redundant. Knockdown of all three isoforms simultaneously was required to alleviate the sphingolipid-mediated inhibition of ceramide biosynthesis. The lipid sensed by the ORMDL-mediated feedback mechanism is medium or long chain ceramide or a higher order sphingolipid. Treatment of permeabilized cells with C6-ceramide resulted in ORMDL-mediated inhibition of the rate-limiting enzyme in sphingolipid biosynthesis, serine palmitoyltransferase. This indicates that C6-ceramide inhibition requires only membrane-bound elements and does not involve diffusible proteins or small molecules. We also tested the atypical sphingomyelin synthase isoform, SMSr, for its role in the regulation of ceramide biosynthesis. This unusual enzyme has been reported to regulate ceramide levels in the endoplasmic reticulum. We were unable to detect a role for SMSr in regulating ceramide biosynthesis. We suggest that the role of SMSr may be in the regulation of downstream metabolism of ceramide.
MeSH term(s)	Ceramides/biosynthesis ; Feedback, Physiological ; HeLa Cells ; Humans ; Membrane Proteins/genetics ; Membrane Proteins/metabolism
Chemical Substances	Ceramides ; Membrane Proteins ; ORMDL1 protein, human ; ORMDL2 protein, human ; ORMDL3 protein, human
Language	English
Publishing date	2012-10-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.C112.404012
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Article ; Online: Dynamics of sphingolipids and the serine palmitoyltransferase complex in rat oligodendrocytes during myelination.

Davis, Deanna L / Mahawar, Usha / Pope, Victoria S / Allegood, Jeremy / Sato-Bigbee, Carmen / Wattenberg, Binks W

Journal of lipid research

2020 Volume 61, Issue 4, Page(s) 505–522

Abstract: Myelin is a unique lipid-rich membrane structure that accelerates neurotransmission and supports neuronal function. Sphingolipids are critical myelin components. Yet sphingolipid content and synthesis have not been well characterized in oligodendrocytes, ...

Abstract	Myelin is a unique lipid-rich membrane structure that accelerates neurotransmission and supports neuronal function. Sphingolipids are critical myelin components. Yet sphingolipid content and synthesis have not been well characterized in oligodendrocytes, the myelin-producing cells of the CNS. Here, using quantitative real-time PCR, LC-MS/MS-based lipid analysis, and biochemical assays, we examined sphingolipid synthesis during the peak period of myelination in the postnatal rat brain. Importantly, we characterized sphingolipid production in isolated oligodendrocytes. We analyzed sphingolipid distribution and levels of critical enzymes and regulators in the sphingolipid biosynthetic pathway, with focus on the serine palmitoyltransferase (SPT) complex, the rate-limiting step in this pathway. During myelination, levels of the major SPT subunits increased and oligodendrocyte maturation was accompanied by extensive alterations in the composition of the SPT complex. These included changes in the relative levels of two alternative catalytic subunits, SPTLC2 and -3, in the relative levels of isoforms of the small subunits, ssSPTa and -b, and in the isoform distribution of the SPT regulators, the ORMDLs. Myelination progression was accompanied by distinct changes in both the nature of the sphingoid backbone and the N-acyl chains incorporated into sphingolipids. We conclude that the distribution of these changes among sphingolipid family members is indicative of a selective channeling of the ceramide backbone toward specific downstream metabolic pathways during myelination. Our findings provide insights into myelin production in oligodendrocytes and suggest how dysregulation of the biosynthesis of this highly specialized membrane could contribute to demyelinating diseases.
MeSH term(s)	Animals ; Brain/cytology ; Brain/metabolism ; Female ; Myelin Sheath/physiology ; Oligodendroglia/metabolism ; Rats ; Rats, Sprague-Dawley ; Serine C-Palmitoyltransferase/metabolism ; Sphingolipids/metabolism
Chemical Substances	Sphingolipids ; Serine C-Palmitoyltransferase (EC 2.3.1.50)
Language	English
Publishing date	2020-02-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80154-9
ISSN	1539-7262 ; 0022-2275
ISSN (online)	1539-7262
ISSN	0022-2275
DOI	10.1194/jlr.RA120000627
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Zs.A 175: Show issues

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Article: Microscopic histochemical demonstration of steroid-3 beta-ol dehydrogenase in tissue sections.

WATTENBERG, L W

The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society

2003 Volume 6, Issue 4, Page(s) 225–232

MeSH term(s)	Humans ; Oxidoreductases/analysis
Chemical Substances	Oxidoreductases (EC 1.-)
Language	English
Publishing date	2003-05-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	218208-7
ISSN	1551-5044 ; 0022-1554
ISSN (online)	1551-5044
ISSN	0022-1554
DOI	10.1177/6.4.225
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Uc I Zs.321: Show issues

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Article: In situ indicator technic, a new principle in histochemical localization of enzymes.

WATTENBERG, L W

Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)

2003 Volume 87, Issue 3, Page(s) 535–538

MeSH term(s)	Biological Phenomena ; Enzymes/analysis ; Physiological Phenomena
Chemical Substances	Enzymes
Language	English
Publishing date	2003-09-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	4015-0
ISSN	1535-3699 ; 1525-1373 ; 0037-9727
ISSN (online)	1535-3699 ; 1525-1373
ISSN	0037-9727
DOI	10.3181/00379727-87-21436
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Ua VI Zs.111: Show issues

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Article: Chemoprevention of pulmonary carcinogenesis by myo-inositol.

Wattenberg, L W

Anticancer research

1999 Volume 19, Issue 5A, Page(s) 3659–3661

Abstract: This abstract summarizes material presented at the "First International Symposium on Disease Prevention by IP6 and other Rice Components "held in Kyoto, Japan in June, 1998. The presentation deals primarily with studies of chemoprevention of pulmonary ... ...

Abstract	This abstract summarizes material presented at the "First International Symposium on Disease Prevention by IP6 and other Rice Components "held in Kyoto, Japan in June, 1998. The presentation deals primarily with studies of chemoprevention of pulmonary carcinogenesis by myo-inositol. This compound is largely formed by the dephosphorylation of inositol hexaphosphate (IP6, phytate) within the gastrointestinal tract in humans and animals. myo-Inositol is one of a relatively few compounds that has an inhibitory effect on carcinogenesis of the lung in experimental animals when administered during the post-initiation period. It prevents pulmonary adenoma formation in A/J mice when fed in the diet subsequent to administrations of benzo[a]pyrene or the tobacco specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) to the mice. A second compound, dexamethasone, also prevents pulmonary neoplasia under the same conditions. Experiments in which both myo-inositol and dexamethasone were administered together in the diet showed an additive inhibitory effect. The significance and utility of the chemopreventive properties of these agents remains to be determined.
MeSH term(s)	Animals ; Anticarcinogenic Agents/therapeutic use ; Dexamethasone/therapeutic use ; Humans ; Inositol/therapeutic use ; Lung Neoplasms/prevention & control ; Mice
Chemical Substances	Anticarcinogenic Agents ; Inositol (4L6452S749) ; Dexamethasone (7S5I7G3JQL)
Language	English
Publishing date	1999-09
Publishing country	Greece
Document type	Journal Article
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
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Zs.A 1642: Show issues

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Article: Mucolytic enzyme systems; effects of tissue extracts and body fluids, certain steroids, and hemoglobin derivatives on hyaluronidase activity.

WATTENBERG, L W / GLICK, D

The Journal of biological chemistry

2007 Volume 179, Issue 3, Page(s) 1213–1228

MeSH term(s)	Body Fluids ; Enzymes ; Expectorants ; Hemoglobins ; Hyaluronoglucosaminidase ; Steroids ; Tissue Extracts
Chemical Substances	Enzymes ; Expectorants ; Hemoglobins ; Steroids ; Tissue Extracts ; Hyaluronoglucosaminidase (EC 3.2.1.35)
Language	English
Publishing date	2007-12-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
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Article: An assay system for measuring the acute production of sphingosine 1-phosphate in intact monolayers.

Siow, Deanna L / Wattenberg, Binks W

Analytical biochemistry

2007 Volume 371, Issue 2, Page(s) 184–193

Abstract: Sphingosine kinase (SK) is a signaling enzyme that phosphorylates sphingosine to produce sphingosine 1-phosphate. Sphingosine and sphingosine 1-phosphate (S1P) belong to a class of bioactive sphingolipid metabolites that are critical in a number of ... ...

Abstract	Sphingosine kinase (SK) is a signaling enzyme that phosphorylates sphingosine to produce sphingosine 1-phosphate. Sphingosine and sphingosine 1-phosphate (S1P) belong to a class of bioactive sphingolipid metabolites that are critical in a number of cellular processes, yet often have opposing biological functions. The intracellular localization of sphingosine kinase has been demonstrated in multiple studies to be a critical aspect of its signaling function. To date, assays of sphingosine kinase activity have been developed for measuring activity in lysates, where the effects of localization are lost. Here we outline a system in which the rate of production of S1P can be measured in intact cells using exogenously added radiolabeled ATP instead of tritiated sphingosine. The surprising ability of ATP to enter unpermeabilized monolayers is one aspect that makes this assay simple, efficient, and inexpensive, yet sensitive enough to measure endogenous enzyme activity. The assay is well behaved in terms of kinetics and substrate dependence. Overall, this assay is ideal for future studies to identify changes in S1P production in intact cells such as those that result from the differential intracellular targeting of sphingosine kinase.
MeSH term(s)	Adenosine Triphosphate/metabolism ; Cells, Cultured ; Chromatography, Thin Layer ; HeLa Cells ; Humans ; Kinetics ; Lysophospholipids/analysis ; Lysophospholipids/biosynthesis ; Phosphorus Radioisotopes ; Phosphotransferases (Alcohol Group Acceptor)/metabolism ; Sensitivity and Specificity ; Sphingosine/analogs & derivatives ; Sphingosine/analysis ; Sphingosine/biosynthesis ; Sphingosine/metabolism ; Unilamellar Liposomes/metabolism
Chemical Substances	Lysophospholipids ; Phosphorus Radioisotopes ; Unilamellar Liposomes ; sphingosine 1-phosphate (26993-30-6) ; Adenosine Triphosphate (8L70Q75FXE) ; Phosphotransferases (Alcohol Group Acceptor) (EC 2.7.1.-) ; sphingosine kinase (EC 2.7.1.-) ; Sphingosine (NGZ37HRE42)
Language	English
Publishing date	2007-12-15
Publishing country	United States
Document type	Evaluation Studies ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1110-1
ISSN	1096-0309 ; 0003-2697
ISSN (online)	1096-0309
ISSN	0003-2697
DOI	10.1016/j.ab.2007.08.002
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Zs.A 389: Show issues

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Article ; Online: Implementation of Semiautomated Antimicrobial Susceptibility Interpretation Hardware for Nontuberculous Mycobacteria May Overestimate Susceptibility.

Rockland, Mariëlle / Ruth, Mike Marvin / Aalders, Nicole / Pennings, Lian / Hoefsloot, Wouter / Wattenberg, Melanie / van Ingen, Jakko

Journal of clinical microbiology

2019 Volume 57, Issue 4

Abstract: Nontuberculous mycobacteria (NTM) cause severe opportunistic infections and have a rising incidence in most settings. Rising diagnostic need must be met by national reference laboratories, which rely on Clinical and Laboratory Standards Institute (CLSI) ... ...

Abstract	Nontuberculous mycobacteria (NTM) cause severe opportunistic infections and have a rising incidence in most settings. Rising diagnostic need must be met by national reference laboratories, which rely on Clinical and Laboratory Standards Institute (CLSI) guideline-approved manual readout of microtiter plates for antimicrobial susceptibility testing (AST) to determine antibiotic minimum inhibitory concentrations (MICs). Interpretation of these plates leads to different outcomes between laboratories. The SensiTitre Vizion digital MIC viewing system (Vizion) offers a more streamlined approach using semiautomated reading. Here, we conducted a blinded trial comparing the outcome of AST between manual readout and Vizion readout for 132 NTM isolates, amounting to 727 individual tests for antibiotic susceptibility ranging across 13 individual antibiotics with established CLSI breakpoints. From this, we calculated specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) and the F1 value, as well as assessing major error (ME) and very major error (VME) rates. We find that Vizion-assisted AST produces significantly lower MICs (paired Wilcox signed rank test;
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Humans ; Microbial Sensitivity Tests/instrumentation ; Microbial Sensitivity Tests/standards ; Mycobacterium Infections, Nontuberculous/diagnosis ; Mycobacterium Infections, Nontuberculous/microbiology ; Nontuberculous Mycobacteria/drug effects ; Nontuberculous Mycobacteria/isolation & purification ; Sensitivity and Specificity
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2019-03-28
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	390499-4
ISSN	1098-660X ; 0095-1137
ISSN (online)	1098-660X
ISSN	0095-1137
DOI	10.1128/JCM.01756-18
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