AI Article Synopsis
Article Abstract
We investigated the effects of sphingosine 1-phosphate and histamine on the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin, and their signaling pathways in human umbilical vein endothelial cells. Sphingosine 1-phosphate increased the mRNA and protein level of VCAM-1, and the mRNAs of E-selectin and ICAM-1. The effects of sphingosine 1-phosphate were inhibited by the pertussis toxin and the respective inhibitors (10 microM 1-[6-[[(17beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122) for phosphoinositide-specific phospholipase C; 10 microM 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole (SB203580) for p38 mitogen-activated protein kinase (MAPK); 1 microM 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3,4-c)-carbazole (Gö6976) for the alpha form of protein kinase C (PKC-alpha)), but not by a PKC-delta inhibitor (1 microM rottlerin). Histamine, which alone showed no effect, enhanced the sphingosine 1-phosphate-induced expressions via histamine H(1) receptor. The histamine response decreased by U73122 and rottlerin, but not by SB203580 and Gö6976. The effects of sphingosine 1-phosphate with and without histamine were abolished by the higher concentrations of PKC inhibitors and in the PKC-depleted cells. Sphingosine 1-phosphate and histamine alone stimulated phosphorylation of p38 MAPK in a phosphoinositide-specific phospholipase C-dependent but not in a PKCs-independent manner. These findings suggest that sphingosine 1-phosphate-induced expression of adhesion molecules was mediated by phosphoinositide-specific phospholipase C and preferentially by PKC-alpha and p38 MAPK, and the histamine response was mediated by phosphoinositide-specific phospholipase C and PKC-delta in human umbilical vein endothelial cells.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejphar.2003.12.022 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Two-Step Cell Death Induction by the New 2-Arachidonoyl Glycerol Analog and Its Modulation by Lysophosphatidylinositol in Human Breast Cancer Cells.
Int J Mol Sci
January 2025
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia.
2-arachnadoyl glycerol (2-AG) is one of the most common endocannabinoid molecules with anti-proliferative, cytotoxic, and pro-proliferative effects on different types of tumors. Typically, it induces cell death via cannabinoid receptor 1/2 (CB1/CB2)-linked ceramide production. In breast cancer, ceramide is counterbalanced by the sphingosine-1-phosphate, and thus the mechanisms of 2-AG influence on proliferation are poorly understood.
View Article and Find Full Text PDFDon't Be Surprised When These Surprise You: Some Infrequently Studied Sphingoid Bases, Metabolites, and Factors That Should Be Kept in Mind During Sphingolipidomic Studies.
Int J Mol Sci
January 2025
School of Biological Sciences and The Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Sphingolipidomic mass spectrometry has provided valuable information-and surprises-about sphingolipid structures, metabolism, and functions in normal biological processes and disease. Nonetheless, many noteworthy compounds are not routinely determined, such as the following: most of the sphingoid bases that mammals biosynthesize de novo other than sphingosine (and sometimes sphinganine) or acquire from exogenous sources; infrequently considered metabolites of sphingoid bases, such as N-(methyl)-derivatives; "ceramides" other than the most common N-acylsphingosines; and complex sphingolipids other than sphingomyelins and simple glycosphingolipids, including glucosyl- and galactosylceramides, which are usually reported as "monohexosylceramides". These and other subspecies are discussed, as well as some of the circumstances when they are likely to be seen (or present and missed) due to experimental conditions that can influence sphingolipid metabolism, uptake from the diet or from the microbiome, or as artifacts produced during extraction and analysis.
View Article and Find Full Text PDF[Not Available].
Gastroenterol Hepatol
January 2025
Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
Etrasimod is a synthetic, non-biological, orally administered small molecule sphingosine-1-phosphate receptor (S1PR) modulator. Etrasimod was approved by the Food and Drug Administration in 2023 and by the European Medicine Agency in 2024, constituting a new therapeutic option for the treatment of moderately to severely active ulcerative colitis in patients 16 years of age and older in the European Union. Its efficacy and tolerability have been demonstrated in several clinical trials both as induction and maintenance treatment, as well as in long-term extension studies.
View Article and Find Full Text PDFActivation of S1PR2 on macrophages and the hepatocyte S1PR2/RhoA/ROCK1/MLC2 pathway in vanishing bile duct syndrome.
PLoS One
January 2025
Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Immunologic bile duct destruction is a pathogenic condition associated with vanishing bile duct syndrome (VBDS) after liver transplantation and hematopoietic stem-cell transplantation. As the bile acid receptor sphingosine 1-phosphate receptor 2 (S1PR2) plays a critical role in recruitment of bone marrow-derived monocytes/macrophages to sites of cholestatic liver injury, S1PR2 expression was examined using cultured macrophages and patient tissues. Bile canaliculi destruction precedes intrahepatic ductopenia; therefore, we focused on hepatocyte S1PR2 and the downstream RhoA/Rho kinase 1 (ROCK1) signaling pathway and bile canaliculi alterations using three-dimensional hepatocyte culture models that form obvious bile canaliculus-like networks.
View Article and Find Full Text PDFMolecular Mechanism and Research Progress of Sphingolipid Metabolism in Regulating Radiation-induced Apoptosis Using Pan-cancer Analysis.
Curr Cancer Drug Targets
January 2025
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Radiotherapy stands as a cornerstone in cancer therapy, with nuclear DNA acknowledged as the principal target molecule for radiation-induced cellular demise or injury. Nonetheless, an expanding body of contemporary research elucidates the significant contri-bution of sphingolipids to radiation-induced cell death, particularly in modulating radiation-induced apoptosis. Radiation can instigate apoptosis through multiple pathways of sphin-golipid metabolism, encompassing the activation of ceramide synthase, acid sphingomyelin-ase, neutral sphingomyelinase, sphingosine-1-phosphate lyase, and sphingosine-1-phosphate phosphatase, and the inhibition of sphingosine kinase-1.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!