The enzymes that catalyze formation of the bioactive sphingolipid, sphingosine 1-phosphate, sphingosine kinase 1 and 2, are predictive markers in inflammatory diseases and cancer as evidenced by data from patients, knockout mice and the use of available molecular and chemical inhibitors. Thus, there is a compelling case for therapeutic targeting of sphingosine kinase. In addition, there are several examples of functional interaction between sphingosine 1-phosphate receptors and sphingosine kinase 1 that can drive malicious amplification loops that promote cancer cell growth. These novel aspects of sphingosine 1-phosphate pathobiology are reviewed herein.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jbior.2013.08.005 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Molecular 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 PDFActivating transcription factor-3 orchestrates the modulation of vascular anti-contractile activity and relaxation by governing the secretion of HDL-bound sphingosine-1-phosphate in perivascular adipose tissue.
Br J Pharmacol
January 2025
Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
Background And Purpose: Perivascular adipose tissues (PVATs) play a critical role in modulating vascular homeostasis and protecting against cardiovascular dysfunction-mediated blood pressure dysregulation. We demonstrated that the activating transcription factor-3 (Atf3) gene in the PVAT is crucial for improving vascular wall tension abnormalities; however, its protective mechanism remains unclear. Herein, we aim to determine whether ATF3 regulates PVAT-derived relaxing factor (PVDRF) biosynthesis and if its secretion contributes to vasorelaxation.
View Article and Find Full Text PDFSphingosine-1-Phosphate, a Marker of Endothelial Injury and Disease Severity in Preeclampsia.
Hypertension
January 2025
Division of Obstetrics and Gynecology, Institute of Clinical Sciences Lund, Lund University, Sweden. (C.E., F.P., L.E., S.R.H.).
Background: Preeclampsia is a hypertensive pregnancy disorder marked by endothelial damage. Healthy endothelium is covered by a protective glycocalyx layer, which, when degraded, releases detectable products into the blood. Sphingosine-1-phosphate (S1P) is a cardiovascular biomarker involved in glycocalyx preservation, linked to placentation and preeclampsia development.
View Article and Find Full Text PDFAnti-ceramide antibody and sphingosine-1-phosphate as potential biomarkers of unresectable non-small cell lung cancer.
Pathol Oncol Res
January 2025
Department of Pulmonology, Semmelweis University, Budapest, Hungary.
Objectives: Spingosine-1-phosphate (S1P) and ceramides are bioactive sphingolipids that influence cancer cell fate. Anti-ceramide antibodies might inhibit the effects of ceramide. The aim of this study was to assess the potential role of circulating S1P and anti-ceramide antibody as biomarkers in non-small cell lung cancer (NSCLC).
View Article and Find Full Text PDFS1PR3-driven positive feedback loop sustains STAT3 activation and keratinocyte hyperproliferation in psoriasis.
Cell Death Dis
January 2025
State Key Laboratory of Analytical Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, 210093, Nanjing, P.R. China.
Psoriasis is a chronic inflammatory skin disorder characterized by hyperproliferation of keratinocytes and persistent inflammation. Although persistent activation of signal transducer and activator of transcription 3 (STAT3) is implicated in its pathogenesis, the mechanisms underlying the sustained STAT3 activation remain poorly understood. Here, we identify sphingosine-1-phosphate receptor 3 (S1PR3) as a critical regulator of STAT3 activation and psoriasis pathogenesis, orchestrating a self-amplifying circuit that sustains keratinocyte hyperproliferation and chronic inflammation.
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!