scholarly journals Sphingolipid Signature of Human Feto-Placental Vasculature in Preeclampsia

2020 ◽  
Vol 21 (3) ◽  
pp. 1019
Author(s):  
Ilaria Del Gaudio ◽  
Linda Sasset ◽  
Annarita Di Lorenzo ◽  
Christian Wadsack
Keyword(s):  
Gene Expression ◽  
Vascular Function ◽  
Direct Contact ◽  
Maternal Plasma ◽  
Serine Palmitoyltransferase ◽  
Immunofluorescence Analysis ◽  
Intrauterine Environment ◽  
Sphingosine 1 Phosphate ◽  
Bioactive Sphingolipids

Bioactive sphingolipids are emerging as key regulators of vascular function and homeostasis. While most of the clinical studies have been devoted to profile circulating sphingolipids in maternal plasma, little is known about the role of the sphingolipid at the feto-placental vasculature, which is in direct contact with the offspring circulation. Our study aims to compare the sphingolipid profile of normal with preeclamptic (PE) placental chorionic arteries and isolated endothelial cells, with the goal of unveiling potential underlying pathomechanisms in the vasculature. Dihydrosphingosine and sphingomyelin (SM) concentrations (C16:0-, C18:0-, and C24:0- sphingomyelin) were significantly increased in chorionic arteries of preeclamptic placentas, whereas total ceramide, although showing a downward trend, were not statistically different. Moreover, RNA and immunofluorescence analysis showed impaired sphingosine-1-phosphate (S1P) synthesis and signaling in PE vessels. Our data reveal that the exposure to a deranged maternal intrauterine environment during PE alters the sphingolipid signature and gene expression on the fetal side of the placental vasculature. This pathological remodeling consists in increased serine palmitoyltransferase (SPT) activity and SM accrual in PE chorionic arteries, with concomitance impairment endothelial S1P signaling in the endothelium of these vessels. The increase of endothelial S1P phosphatase, lyase and S1PR2, and blunted S1PR1 expression support the onset of the pathological phenotype in chorionic arteries.

scholarly journals The Sphingolipid Asset Is Altered in the Nigrostriatal System of Mice Models of Parkinson’s Disease

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 93
Author(s):  
Victor Blokhin ◽  
Maria Shupik ◽  
Ulyana Gutner ◽  
Ekaterina Pavlova ◽  
Albert T. Lebedev ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sphingolipid Metabolism ◽  
Nigrostriatal System ◽  
Dopaminergic Cell ◽  
Metabolism Enzymes ◽  
Clinical Stages ◽  
Sphingosine 1 Phosphate

Parkinson’s disease (PD) is a neurodegenerative disease incurable due to late diagnosis and treatment. Therefore, one of the priorities of neurology is to study the mechanisms of PD pathogenesis at the preclinical and early clinical stages. Given the important role of sphingolipids in the pathogenesis of neurodegenerative diseases, we aimed to analyze the gene expression of key sphingolipid metabolism enzymes (ASAH1, ASAH2, CERS1, CERS3, CERS5, GBA1, SMPD1, SMPD2, UGCG) and the content of 32 sphingolipids (subspecies of ceramides, sphingomyelins, monohexosylceramides and sphinganine, sphingosine, and sphingosine-1-phosphate) in the nigrostriatal system in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse models of the preclinical and clinical stages of PD. It has been shown that in PD models, the expression of five of the nine studied genes (CERS1, CERS5, ASAH1, ASAH2, and GBA1) increases but only in the substantia nigra (SN) containing dopaminergic cell bodies. Changes in the expression of enzyme genes were accompanied by an increase in the content of 7 of the 32 studied sphingolipids. Such findings suggest these genes as attractive candidates for diagnostic purposes for preclinical and clinical stages of PD.

Abstract P212: Sphingolipid De Novo Pathway is a Novel Regulator of Blood Pressure Homeostasis

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Anna Cantalupo ◽  
Yi Zhang ◽  
Xian-Cheng Jiang ◽  
Annarita Di Lorenzo
Keyword(s):  
Blood Pressure ◽  
Endothelial Cells ◽  
High Blood Pressure ◽  
Vascular Reactivity ◽  
De Novo ◽  
Ex Vivo ◽  
Mesenteric Arteries ◽  
Serine Palmitoyltransferase ◽  
Sphingosine 1 Phosphate

Background and objectives: Sphingolipids, particularly sphingosine 1-phosphate (S1P), play an important role in the cardiovascular homeostasis. Recently, we revealed that endothelial de novo biosynthesis of sphingolipids is very important to control vascular functions and blood pressure. We discovered that in blood vessels, particularly in endothelial cells, Nogo-B, a membrane protein of the endoplasmic reticulum, inhibits serine palmitoyltransferase (SPT), the first and rate-limiting enzyme of de novo production of sphingolipids, to impact vascular tone and blood pressure. Indeed, mice lacking Nogo-B are protected from angiotensin II-induced hypertension, and pharmacological inhibition of SPT by myriocin reinstates high blood pressure in absence of Nogo-B, suggesting that the upregulation of SPT activity exerts anti-hypertensive functions. Thus, the goal of this study is to investigate the role of SPT in vascular functions and blood pressure regulation by using novel genetic mouse models. Methods: The SBP was evaluated in 14 weeks old mice heterozygous for Sptlc2 ( Sptlc2 +/- ) or lacking Sptlc2 specifically in endothelial cells (ECKO Sptlc2 ) and smooth muscle cells (SMCKO Sptlc2 ) by using tail-cuff system. Vascular reactivity of isolated mesenteric arteries was assessed ex-vivo by using the pressure myograph system. Results: Sptlc2 +/- , ECKO Sptlc2 and SMCKO Sptlc2 mice were hypertensive compared to their respective controls ( Sptlc2 +/- 128.9±2.6 vs. WT 112.1±2.6 mmHg; ECKO Sptlc2 125.5±1.8, SMCKO Sptlc2 127.2±0.6 vs. Sptlc2 f/f 106±0.84 mmHg) and developed endothelial dysfunction as shown by the impaired vasodilation in response to acetylcholine (EC 50 Sptlc2 +/- 1.48x10 -6 M vs. WT 4.46x10 -7 M; Emax ECKO Sptlc2 73.2±3.3% vs. Sptlc2 f/f 95.3±1.1%), as well as to flow (Emax: Sptlc2 +/- 23.3±1.4 μm vs. WT 42.9±4.4 μm; ECKO Sptlc2 19.9±0.9 μm vs. Sptlc2 f/f 41.3±3.1 μm). Conclusion: This study demonstrates the important role of SPT, thus the de novo production of sphingolipids, in controlling blood flow and pressure homeostasis, and provides the ground for the development of alternative therapeutic strategies to manage high blood pressure.

scholarly journals Nuclear lipid mediators: Role of nuclear sphingolipids and sphingosine‐1‐phosphate signaling in epigenetic regulation of inflammation and gene expression

2018 ◽  
Vol 119 (8) ◽  
pp. 6337-6353 ◽  
Author(s):  
Panfeng Fu ◽  
David L. Ebenezer ◽  
Alison W. Ha ◽  
Vidyani Suryadevara ◽  
Anantha Harijith ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epigenetic Regulation ◽  
Lipid Mediators ◽  
Sphingosine 1 Phosphate

Role of small nuclear RNAs in eukaryotic gene expression

2013 ◽  
Vol 54 ◽  
pp. 79-90 ◽  
Author(s):  
Saba Valadkhan ◽  
Lalith S. Gunawardane
Keyword(s):  
Gene Expression ◽  
Protein Interactions ◽  
Rna Stability ◽  
Splice Sites ◽  
Branch Site ◽  
Small Nuclear Rnas ◽  
Eukaryotic Gene Expression ◽  
Eukaryotic Gene ◽  
Rna Biogenesis

Eukaryotic cells contain small, highly abundant, nuclear-localized non-coding RNAs [snRNAs (small nuclear RNAs)] which play important roles in splicing of introns from primary genomic transcripts. Through a combination of RNA–RNA and RNA–protein interactions, two of the snRNPs, U1 and U2, recognize the splice sites and the branch site of introns. A complex remodelling of RNA–RNA and protein-based interactions follows, resulting in the assembly of catalytically competent spliceosomes, in which the snRNAs and their bound proteins play central roles. This process involves formation of extensive base-pairing interactions between U2 and U6, U6 and the 5′ splice site, and U5 and the exonic sequences immediately adjacent to the 5′ and 3′ splice sites. Thus RNA–RNA interactions involving U2, U5 and U6 help position the reacting groups of the first and second steps of splicing. In addition, U6 is also thought to participate in formation of the spliceosomal active site. Furthermore, emerging evidence suggests additional roles for snRNAs in regulation of various aspects of RNA biogenesis, from transcription to polyadenylation and RNA stability. These snRNP-mediated regulatory roles probably serve to ensure the co-ordination of the different processes involved in biogenesis of RNAs and point to the central importance of snRNAs in eukaryotic gene expression.

Cell-specific regulation of IRS-1 gene expression: role of E box and C/EBP binding site in HepG2 cells and CHO cells

Diabetes ◽  
1997 ◽  
Vol 46 (3) ◽  
pp. 354-362 ◽  
Author(s):  
K. Matsuda ◽  
E. Araki ◽  
R. Yoshimura ◽  
K. Tsuruzoe ◽  
N. Furukawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Site ◽  
Cho Cells ◽  
Hepg2 Cells ◽  
E Box ◽  
Specific Regulation
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