Ceramides and sphingoid long-chain bases (LCBs) are precursors to more complex sphingolipids and play distinct signaling roles crucial for cell growth and survival. Conserved reactions within the sphingolipid biosynthetic pathway are responsible for the formation of these intermediates. Components of target of rapamycin complex 2 (TORC2) have been implicated in the biosynthesis of sphingolipids in S. cerevisiae; however, the precise step regulated by this complex remains unknown. Here we demonstrate that yeast cells deficient in TORC2 activity are impaired for de novo ceramide biosynthesis both in vivo and in vitro. We find that TORC2 regulates this step in part by activating the AGC kinase Ypk2 and that this step is antagonized by the Ca2+/calmodulin-dependent phosphatase calcineurin. Because Ypk2 is activated independently by LCBs, the direct precursors to ceramides, our data suggest a model wherein TORC2 signaling is coupled with LCB levels to control Ypk2 activity and, ultimately, regulate ceramide formation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3882310 | PMC |
| http://dx.doi.org/10.1016/j.cmet.2007.11.015 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
High temperature ameliorates high-fat diet-induced obesity by promoting ceramide breakdown in skeletal muscle tissue.
Life Metab
October 2024
Key Laboratory of Agriculture Animal Genetics, Breeding and Reproduction of the Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
Obesity is considered an epidemic often accompanied by insulin resistance (IR). Heat treatment (HT) has been shown to prevent high-fat diet-induced IR in skeletal muscle, but the underlying mechanisms are poorly understood. In this study, we discovered that high temperature alleviated the hallmarks of obesity by promoting glycogen synthesis and lowering blood glucose levels in skeletal muscle tissue (SMT).
View Article and Find Full Text PDFLysophosphatidylcholine induces ceramide synthase-2 expression in primary culture model of astrocytopathy: potential therapeutic target in multiple sclerosis.
Mol Biol Rep
January 2025
Department of Pharmacology, School of Health Sciences, Central University of Punjab, Bathinda, 151401, India.
Background: Multiple sclerosis (MS) is a chronic autoimmune condition that damages the myelin sheath of neurons in the central nervous system, resulting in compromised nerve transmission and motor impairment. The astrocytopathy is considered one of the prominent etiological factor in the pathophysiology of demyelination in MS. The expression level of ceramide synthase-2 (CS-2) is yet to be established in the pathophysiology of astrocytopathy although the derailed ceramide biosynthetic pathways is well demonstrated in the pathophysiology of demyelination.
View Article and Find Full Text PDFPreviously, our metabolomic, transcriptomic, and genomic studies characterized the ceramide/sphingomyelin pathway as a therapeutic target in Alzheimer's disease, and we demonstrated that FTY720, a sphingosine-1-phospahate receptor modulator approved for treatment of multiple sclerosis, recovers synaptic plasticity and memory in APP/PS1 mice. To further investigate how FTY720 rescues the pathology, we performed metabolomic analysis in brain, plasma, and liver of trained APP/PS1 and wild-type mice. APP/PS1 mice showed area-specific brain disturbances in polyamines, phospholipids, and sphingolipids.
View Article and Find Full Text PDFIntegrating the GRACE Score with the Ceramide Risk Score Enhances the Predictive Accuracy of Major Adverse Cardiac Events in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.
Rev Cardiovasc Med
January 2025
Department of Cardiology, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, China.
Background: Ceramide, a key molecule in sphingolipid metabolism, is recognized as a standalone predictor of long-term major adverse cardiac events (MACE). We explore if integrating the global registry of acute coronary events (GRACE) score with the ceramide risk score (ceramide test 1, CERT1) improves MACE prediction in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).
Methods: This cohort study included 210 participants with ACS undergoing PCI.
Integrated metabolomics and mass spectrometry imaging analysis reveal the efficacy and mechanism of Huangkui capsule on type 2 diabetic nephropathy.
Phytomedicine
January 2025
State key laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China; Department of Nephrology, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China. Electronic address:
Background: Huangkui capsule (HKC), a Chinese patent medicine, is clinically used for treating diabetic nephropathy. However, the core disease-specific biomarkers and targets of type 2 diabetic nephropathy (T2DN) and the therapeutic mechanism of HKC are not fully elucidated.
Purpose: This study aimed to investigate the therapeutic effects and underlying molecular mechanisms of HKC for T2DN.
Want 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!