A5044308307- Sphingolipid Metabolism and Signaling
- Endoplasmic Reticulum Stress and Disease
- Lysosomal Storage Disorders Research
- Carbohydrate Chemistry and Synthesis
- Cellular transport and secretion
- Pharmacogenetics and Drug Metabolism
- Lipid Membrane Structure and Behavior
- Liver Disease Diagnosis and Treatment
- Signaling Pathways in Disease
- Drug Transport and Resistance Mechanisms
- Cardiac electrophysiology and arrhythmias
- Research on Leishmaniasis Studies
- EEG and Brain-Computer Interfaces
- Functional Brain Connectivity Studies
- Breast Cancer Treatment Studies
- Cancer-related Molecular Pathways
- Opioid Use Disorder Treatment
- Erythrocyte Function and Pathophysiology
- Lipid metabolism and biosynthesis
- Advanced Breast Cancer Therapies
- Anesthesia and Pain Management
- Polysaccharides and Plant Cell Walls
- Epilepsy research and treatment
- Diet, Metabolism, and Disease
- Venous Thromboembolism Diagnosis and Management
Stony Brook University
2014-2025
State University of New York
2013-2025
Nanjing Drum Tower Hospital
2017-2024
Third Affiliated Hospital of Zhengzhou University
2021-2023
Zhumadian Central Hospital
2023
Sichuan University
2022
Southern Medical University
2022
Nanfang Hospital
2022
Nanjing University
2015
Medical University of South Carolina
2000-2011
Ceramide is not only a core intermediate of sphingolipids but also an important modulator many cellular events including apoptosis, cell cycle arrest, senescence, differentiation, and stress responses. Its turnover may be tightly regulated. However, little known about the regulation its metabolism because most enzymes responsible for synthesis breakdown have yet to cloned. Here we report cloning characterization yeast gene <i>YPC1</i> (<i>YBR183w</i>) by screening<i>Saccharomyces cerevisiae...
Ceramidases are enzymes involved in regulating cellular levels of ceramides, sphingoid bases, and their phosphates. Based on sequence homology to the yeast alkaline ceramidases YPC1p (Mao, C., Xu, R., Bielawska, A., Obeid, L. M. (2000) J. Biol. Chem. 275, 6876--6884) YDC1p Szulc, Z. M., Biol 31369--31378), we report identification cloning a cDNA encoding for novel human ceramidase (aPHC) that hydrolyzes phytoceramide selectively. Northern blot analysis showed aPHC was ubiquitously expressed,...
In a previous study, we reported that the Saccharomyces cerevisiae gene YPC1 encodes an alkaline ceramidase with dual activity, catalyzing both hydrolysis and synthesis of yeast ceramide (Mao, C., Xu, R., Bielawska, A., Obeid, L. M. (2000) J. Biol. Chem. 275, 6876-6884). this have identified homologue in S. also ceramidase. We show these two ceramidases different substrate specificity, such YPC1p preferentially hydrolyzes phytoceramide, whereas new YDC1p dihydroceramide phytoceramide only...
Sphingosine-1-phosphate (S1P), a sphingolipid metabolite, promotes cell proliferation and survival whereas its precursor, sphingosine, has the opposite effects. However, much remains unknown about their regulation. Here we identify novel human ceramidase (haCER2) that regulates levels of both sphingosine S1P by controlling hydrolysis ceramides. haCER2 is localized to Golgi complex highly expressed in placenta. High ectopic expression caused fragmentation growth arrest HeLa cells due...
Ceramides with different fatty acyl chains may vary in their physiological or pathological roles; however, it remains unclear how cellular levels of individual ceramide species are regulated. Here, we demonstrate that our previously cloned human alkaline ceramidase 3 (ACER3) specifically controls the hydrolysis ceramides carrying unsaturated long chains, long-chain (ULC) ceramides. In vitro, ACER3 only hydrolyzed C(18:1)-, C(20:1)-, C(20:4)-ceramides, dihydroceramides, and phytoceramides....
We identified two unrelated consanguineous families with three children affected by the rare association of congenital nephrotic syndrome (CNS) diagnosed in first days life, hypogonadism, and prenatally detected adrenal calcifications, associated insufficiency one case. Using exome sequencing targeted Sanger sequencing, homozygous truncating mutations, c.1513C>T (p.Arg505*) c.934delC (p.Leu312Phefs*30), were SGPL1-encoding sphingosine-1-phosphate (S1P) lyase 1. SGPL1 catalyzes irreversible...
Abstract p53 mediates the DNA damage response (DDR) by regulating expression of genes implicated in cell cycle arrest, senescence, programmed death (PCD), and metabolism. Herein we demonstrate that human alkaline ceramidase 2 (ACER2) is a novel transcriptional target its transactivation DDR. We found overexpression or activation ionizing radiation (IR) upregulated ACER2 cells. Two putative responsive elements (p53REs) were first intron gene, Chromatin Immunoprecipitation (ChIP) assays...
Ceramide has been shown to cause anoikis, a subtype of apoptosis due inadequate cell adhesion. However, the underlying mechanism is unclear. Herein, we report that D-e-C 6 -ceramide (D-e-Cer), via generating sphingosine, disrupts Golgi complex (GC), which associated with various cellular effects, including anoikis. Treatment HeLa cells D-e-Cer caused elongation, spreading inhibition, rounding, and detachment before (anoikis). In D-e-Cer–treated cells, glycosylation β1 integrin in GC was...
Dyshomeostasis of both ceramides and sphingosine-1-phosphate (S1P) in the brain has been implicated aging-associated neurodegenerative disorders humans. However, mechanisms that maintain homeostasis these bioactive sphingolipids remain unclear. Mouse alkaline ceramidase 3 (Acer3), which preferentially catalyzes hydrolysis C18:1-ceramide, a major unsaturated long-chain ceramide species brain, is upregulated with age mouse brain. Acer3 knockout causes an age-dependent accumulation various...
<h3>Background/aims</h3> Leukodystrophies due to abnormal production of myelin cause extensive morbidity in early life; their genetic background is still largely unknown. We aimed at reaching a molecular diagnosis Ashkenazi-Jewish patients who suffered from developmental regression 6–13 months, leukodystrophy and peripheral neuropathy. <h3>Methods</h3> Exome analysis, determination alkaline ceramidase activity catalysing the conversion C<sub>18:1</sub>-ceramide sphingosine...
// Ruijuan Xu 1, 2 , Kai Wang Izolda Mileva 3 Yusuf A. Hannun Lina M. Obeid 2, 4 Cungui Mao 1 Department of Medicine, State University New York at Stony Brook, NY 11794, USA Brook Cancer Center, Lipidomics Core Facility, Ralph H. Johnson Veterans Administration Hospital, Correspondence to: Mao, e-mail: cungui.mao@stonybrook.edu Keywords: ceramide, Golgi, p53, programmed cell death, reactive oxygen species Received: September 18, 2015 Accepted: January 29, 2016 Published: March 01, ABSTRACT...
Overload of palmitic acids is linked to the dysregulation ceramide metabolism in nonalcoholic steatohepatitis (NASH), and ceramides are important bioactive lipids mediating lipotoxicity acid NASH. However, much remains unclear about role ceramidases that catalyze hydrolysis By analyzing National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, we found alkaline ceramidase 3 (ACER3) upregulated livers patients with Consistently, Acer3 mRNA levels its...
Ceramidases deacylate ceramides, important intermediates in the metabolic pathway of sphingolipids. In this study, we report cloning and characterization a novel mouse alkaline ceramidase (maCER1) with highly restricted substrate specificity. maCER1 consists 287 amino acids, it has 28 32% identity to Saccharomyces ceramidases (YPC1p YDC1p) human phytoceramidase, respectively. Reverse transcriptase-PCR analysis demonstrated that was predominantly expressed skin. localized endoplasmic...
Increased generation of dihydrosphingosine (DHS), a bioactive sphingolipid, has been implicated in the cytotoxicity synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) tumor cells. However, how 4-HPR increases DHS remains unclear. Here we demonstrate that expression ACER2, which catalyzes hydrolysis dihydroceramides to generate DHS, and ACER2 up-regulation plays key role mediating 4-HPR-induced as well Treatment with induced accumulation (DHCs) cells by inhibiting dihydroceramide...
Plasma sphingosine-1-phosphate (S1P) has been suggested to mainly originate from erythrocytes; however, within the erythrocyte, how sphingosine (SPH) generation—the precursor S1P—is controlled is unknown. SPH only generated hydrolysis of ceramides via ceramidases. Five human ceramidases have identified: 1 acid, neutral, and 3 alkaline (ACER1, ACER2, ACER3). Here, we demonstrate that ceramidase activity expressed in erythrocytes it instrumental for generation. Erythrocytes but not acid or...
Background The Caprini risk assessment model (RAM) is the most commonly used tool for evaluating venous thromboembolism (VTE) risk, a high score arthroplasty can result in patients being classified as VTE. Therefore, its value post-arthroplasty has been subject to debate. Methods Retrospective data were collected from who underwent between August 2015 and December 2021. study cohort included 3,807 patients, all of whom thorough evaluation using RAM vascular Doppler ultrasonography...
Sphingosine-1-phosphate (S1P) plays important roles in cardiovascular development and immunity. S1P is abundant plasma because erythrocytes—the major source of S1P—lack any S1P-degrading activity; however, much remains unclear about the precursor, sphingosine (SPH), derived mainly from hydrolysis ceramides by action ceramidases that are encoded 5 distinct genes, acid ceramidase 1 (ASAH1)/Asah1, ASAH2/Asah2, alkaline (ACER1)/Acer1, ACER2/Acer2, ACER3/Acer3, humans/mice. Previous studies have...